Objective To study the protective effect of silybin on liver tissue and regulation of TGF-β 1/Smad3 signal pathway in thioacetamide induced hepatic fibrosis in rats. Methods 45 rats were randomly divided into control group, model group, silybin group and colchicine group, with 15 rats in each group. Except for the control group, the other rats were treated with thioacetamide to establish the rat model of hepatic fibrosis. The rats in the silybin group were given silibinin according to the dose of 75.6mg/kg. The rats in the control group and model group were given the same amount of normal saline once a day for 6 weeks. The levels of ALT, AST, ALP and GGT in serum were detected by automatic biochemical analyzer, and the levels of HA, LN, PCⅢ and ColⅣ in serum were detected by ELISA method. The pathological changes of liver tissue were detected by hematoxylineosin (HE) staining, and the levels of TGFβ1 and Smad3 in liver tissue were detected by, western blot. Results The serum levels of ALT, AST, ALP, GGT, HA, LN, PCⅢ, ColⅣ and the levels of TGFβ1 and Smad3 in the liver tissue of the model group were significantly higher than those of the control group(P＜0.05), and obvious pathological changes occurred in the liver tissue of the model group. Compared with the model group, the serum levels of ALT, AST, ALP, GGT, HA, LN, PCⅢ, ColⅣ and the levels of TGFβ1 and Smad3 in liver tissue of rats in silybin group were significantly decreased(P＜0.05), and the liver histopathology was significantly improved. Conclusion silybin can significantly improve the liver function of thioacetamideinduced hepatic fibrosis in rats, inhibit the level of hepatic fibrosis factors, and improve the pathological progress of liver tissue in rats. The mechanism may be related to the regulation of TGF-β 1/Smad3 signal pathway.