Abstract：Objective：To observe the effect of semen plantaginis on the expression of AQP3 gene and protein in small intestine tissue of rats with diarrhea，and to explore the mechanism of its treatment of diarrhea. Methods：The rat models with diarrhea were established by intragastric administration of Folium Sennae. Sixty male SD rats were randomly divided into the normal group，the model group，hydrochlorothiazide group and the semen plantaginis groups of low- dose，mediumdose and high- dose. Except for the normal group， all the other groups were given Folium Sennae solution intragastrically every morning，and the normal group was given the same amount of distilled water intragastrically. Each treatment group was given corresponding medicine by gavage every afternoon，while the normal group and the model group were given the same amount of distilled water by gavage. The defecation of rats during the administration period was observed for 14 consecutive days. After the experiment，the loose stool rate，average loose stool grade and diarrhea index of rats in each group were statistically compared according to fecal traits and fecal frequency. Under anesthesia， two small intestine tissues were sected，one of which was placed in cryopreservation tube and cryopreservation with liquid nitrogen for the detection of the expression of AQP3 gene and protein in small intestine by qRT- PCR method and immunohistochemistry； and the other tissue was put in 4% paraformaldehyde solution， and the pathomorphological changes of small intestine mucosa were observed by hematoxylin-eosin(HE) staining. Results：In the model group，the loose stool rate，average loose stool grade and diarrhea index were significantly increased(P＜0.01)； the villous epidermal cells of small intestine were significantly apoptotic and necrotic； the capillary of lamina propria was dilatation and congestion were obvious， and a few neutrophils were infiltrated in the interstitium；the expression levels of AQP3 gene and protein in small intestine tissue were decreased (P＜0.01). Compared with the model group，the loose stool rate，average loose stool grade and diarrhea index of rats in each dose group of semen plantaginis were all decreased(P＜0.01)；apoptosis，necrosis and capillary dilatation and congestion of villous epidermal cells in small intestine were alleviated；there were a few neutrophils infiltrating the stroma；epithelial cell proliferation was observed in the semen plantaginis groups of medium-dose and high-dose；the expression levels of AQP3 gene and protein in small intestine tissue were significantly higher than those in the model group(P＜0.01). Conclusion： Semen plantaginis has antidiarrhoea effect，and its mechanism is related to reducing intestinal mucosal inflammatory injury， upregulating the expression levels of AQP3 gene and protein， increasing intestinal water absorption and regulating water metabolism.