To explore the effect of gentiopicroside (GPS) on hepatic fibrosis (HF) the Sonic hedgehog (Shh) signal pathway of hepatic fibrosis in rats.Forty male SD rats were randomly divided into normal group,model group,colchicine (0.12 mg/kg) group and GPS (100 mg/kg) group with 10 rats in each group.Except for the normal group,the rats in other groups were intraperitoneally injected with 40% CCl₄ olive oil solution (1 mL/kg) twice a week to establish the HF rat model.And from the day of modeling,rats in colchicine group and GPS group were gavaged with corresponding volume of drugs according to body weight,while rats in normal group and model group were fed with corresponding volume of distilled water according to body weight,once a day for 6 weeks.After the last administration,the contents of ALT,AST,TBIL and ALB in serum were detected by biochemical method,and the contents of HA,LN,PC Ⅲ and Ⅳ-C in serum were detected by ELISA.HE staining and Masson staining were used to observe the histopathological changes of rat livers.Immunohistochemical was used to observe expression of α-SMA and TGF-β1 in liver tissues of rats in each group.Expression levels of α-SMA, TGF-β1 and Shh, Gli-l in the Shh signal pathway were detected by Western blot.The results showed that the contents of ALT,AST,TBIL,HA,LN,PC-Ⅲ and Ⅳ-C in serum of HF rats in GPS group and colchicine group decreased significantly,while the content of ALB increased.The pathological sections showed that the pathological changes of HF in the GPS group and colchicine group were significantly less than those in the model group.Expression of α-SMA and TGF-β1 in liver tissues was decreased.The protein expression levels of TGF-β1,α-SMA,Shh and Gli-l in liver tissue were significantly decreased.The results of this study indicated that GPS can significantly improve HF in rats,and the mechanism is related to the inhibition of Shh signal pathway by GPS.