Abstract：Objective：To investigate the effect of chlorogenic acid on the bioactivity of human periodontal ligament cells (hPDLCs) cultured in high glucose environment using hPDLCs cultured in vitro. Methods： For primary culture of hPDLCs， hPDLCs were treated with normal glucose(5.5 mmol/L) or high glucose(25 mmol/L) plus chlorogenic acid (0.5 mg/mL、1 mg/ mL). CCK-8 assay was used to detect the effect of different concentrations of chlorogenic acid on the proliferation ability of hPDLCs under high glucose environment，meanwhile，the expression levels of nuclear factor receptor activating factor κB ligand(RANKL) and osteoprotegerin(OPG) mRNA in hPDLCs were detected by real time fluorescence quantitative PCR (RTqPCR) assay. The expression levels of interleukin-6(IL-6) in hPDLCs were measured by enzyme linkend immunsorbent assay (ELISA). Results： High glucose(25 mmol/L) significantly inhibited hPDLCs proliferation， promoted IL- 6 expression， upregulated RANKL mRNA expression and downregulated OPG mRNA expression in hPDLCs(P＜0.05).However，chlorogenic acid could inhibit IL- 6 expression in hPDLCs under high glucose environment(P＜0.05)， downregulate RANKL mRNA expression in hPDLCs under high glucose environment，while upregulate OPG mRNA expression (P＜0.05)，and improve the inhibitory effect of high glucose on hPDLCs proliferation(P＜0.05). Conclusion：Chlorogenic acid can inhibit IL-6 secretion in hPDLCs， regulate OPG and RANKL mRNA expression in hPDLCs and antagonize the inhibitory effect of high glucose on hPDLCs proliferation.