Abstract：Objective：To observe the effects of ganoderma lucidum polysaccharides （GLPs） on the proliferation and inflammatory factor release of rheumatoid arthritis （RA） fibroblast-like synoviocytes （RA-FLSs）. Methods：After isolating and culturing RA-FLSs in vitro，two experiments were set up：①To observe the effect of interleukin （IL）-17 on the proliferation of RA-FLSs cells，the cells were divided into a negative control group （untreated RA-FLSs），an IL-17 group（ with 5 ng/mL IL-17），and a tumor necrosis factor-α（ TNF-α） group（ with 10 ng/mL TNF-α，a positive control）；②To observe the inhibitory effect of GLPs on the proliferation of RA-FLSs and the expression of IL-1β and IL-6， the cells were divided into a negative control group （untreated RA-FLSs）， an IL-17 group （with 5 ng/mL IL-17）， and an IL-17+GLPs group （with 5 ng/mL IL-17 and 5 ng/mL GLPs）. After 48 h of treatment， the mRNA expression of IL-6 and IL-1β was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Western blot analysis was performed to assess the expression and phosphorylation levels of IL-6, IL-1β，and key components of the mitogen-activated protein kinase/extracellular regulated protein kinase （MAPK/ERK） and Nuclear Factor-kappa B （NF-κB） signaling pathways, specifically p65 and p50. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression levels of IL-6 and IL-1β，with OD450 values representing absorbance changes to reflect the relative differences in cytokine secretion. Cell proliferation was assessed using a CCK-8 assay. Results：① Whether IL-17 can promote the proliferation of RA-FLSs （IL-17 group，TNF-α group，negative control group）：There was no statistically significant difference in OD450 values among the three groups at 0 h （P＞0.05）. At 96 h， there was a statistically significant difference in OD450 values among the three groups （P＜0.05）； the OD450 values of the IL-17 group and TNF-α group were higher than those of the negative control group （P＜0.05），while there was no statistically significant difference in OD450 values between the IL-17 group and the TNF-α group （P＞0.05）. After two weeks in culture，The count of cell colonies in the three groups showed statistically significant differences （P＜0.05）. The count of cell colonies in the IL-17 group and the TNF-α group was more than that in the negative control group （P＜0.05）. There was no statistically significant difference in the count of cell colonies between the IL-17 group and the TNF-α group （P＞0.05）. The relative expression levels of IL-6 and IL-1β mRNA among the three groups showed statistically significant differences （P＜0.05）. The relative expression levels of IL-6 and IL-1β mRNA in the IL-17 group and TNF-α group were higher than those in the negative control group （P＜0.05）. There was no statistically significant difference in the relative expression levels of IL-6 and IL-1β mRNA between the IL-17 group and the TNF- α group（ P＞0.05）. The relative expression levels of IL-6 and IL-1β proteins among the three groups were all statistically significant （P＜0.05）. The relative expression levels of IL-6 and IL-1β proteins in the IL-17 group and the TNF-α group were higher than those in the negative control group （P＜0.05）， while there was no statistically significant difference in the relative expression levels of IL-6 and IL-1β proteins between the IL-17 group and the TNF- α group （P＞0.05）. ②Whether GLPs can inhibit RA-FLSs proliferation （IL-17 group， IL-17+GLPs group， negative control group）：At 0 h，there was no statistically significant difference in OD450 values among the three groups （P＞ 0.05）. At 96 h，the OD450 values of the three groups showed statistically significant differences （P＜0.05）. The OD450 values of the IL-17 group were higher than those of the negative control group and the IL-17+GLPs group （P＜0.05）. There was no statistically significant difference in OD450 values between the IL-17+GLPs group and the negative control group （P＞0.05）. After two weeks in culture， the count of cell colonies in the three groups showed statistically significant differences （P＜0.05）. The count of cell colonies in the IL-17 group was higher than that in the negative control group and the IL-17+GLPs group （P＜0.05）. There was no statistically significant difference in the count of cell colonies between the IL-17+GLPs group and the negative control group （P＞0.05）. The relative expression levels of IL-6 and IL-1β mRNA in the three groups also showed statistically significant differences （P＜0.05）. The relative expression levels of IL-6 and IL-1β mRNA in the IL-17 group were significantly higher than those in the negative control group and the IL-17+GLPs group （P＜0.05）；however，there were no statistically significant differences in the relative expression levels of IL-6 and IL-1β mRNA between the IL-17+GLPs group and the negative control group （P＞0.05）. The relative expression levels of IL-6 and IL-1β proteins in the three groups were statistically significant （P＜0.05）. The relative expression levels of IL-6 and IL-1β proteins in the IL-17 group were significantly higher than those in the negative control group and the IL-17+GLPs group （P＜0.05）； however， there were no statistically significant differences in the relative expression levels of IL-6 and IL-1β proteins between the IL-17+GLPs group and the negative control group （P＞0.05）. ③Western blot results showed that GLPs could inhibit IL-17-induced phosphorylation activation of the MAPK/ERK signaling pathway and the NF-κB signaling pathway. Conclusion：GLPs can effectively antagonize IL-17-induced proliferation and inflammatory factor release in RA-FLSs，with a regulatory effect comparable to that of TNF-α， suggesting that GLPs may be a potential candidate drug for anti-inflammatory therapy in RA.