OBJECTIVE: To study the effects of rabeprazole (RPZ) on in vivo anti-platelet aggregation and metabolism of clopidogrel in rats. METHODS: Totally 40 SD rats were randomly divided into blank control group, RPZ group, CLP group, RPZ+CLP group and CLP+RPZ group, with 8 rats in each group. The dose of CLP and RPZ were 6.75 and 0.9 mg/kg, with medication interval of 2 h, for consecutive 14 d. The maximal platelet aggregation (MPA), platelet reaction index (PRI), gastric mucosal injury score and blood concentration [carboxylic acid of clopidogrel (CA) and active metabolite of clopidogrel (AM) were detected. The relationship of MPA and PRI with CA and AM were analyzed by Pearson relation analysis. RESULTS: Compared with blank control group, MPA and PRI of rats were decreased significantly in CLP group, RPZ+CLP group and CLP+RPZ group (P<0.05). Gastric mucosal injury score was increased significantly (P<0.05), while MPA, PRI and gastric mucosal injury score had no significant change in RPZ group (P>0.05). Compared with CLP group, MPA and PRI were increased significantly in RPZ+CLP group and CLP+RPZ group (P<0.05); gastric mucosal injury score was decreased significantly (P<0.05) and blood concentration of AM was also decreased significantly (P<0.05). Blood concentration of CA in 3 groups had no significant change (P>0.05). MPA and PRI were both negatively related with AM (r=-0.689, -0.765,P<0.05), while they had no significant correlation with CA (r=-0.117, 0.048, P>0.05). CONCLUSIONS: RPZ can inhibit the antiplatelet effect of CLP and CLP-induced gastric mucosal injury, and medication order of two drugs doesn’t influence CLP metabolism.