Background and Aims Liver fibrosis is a pathological reaction of a series of fibrous tissue proliferation in the liver, and it may cause insufficient or failed regeneration of the liver after hepatectomy. This study was conducted to investigate the effects of transforming growth factor β (TGF-β) pathway on liver function and liver regeneration in animal models of liver fibrosis after partial liver resection, and the possible mechanism.Methods Liver fibrosis was induced by intraperitoneal injection of CCl₄ in 40 SD rats. Then, 32 of them underwent 70% partial resection of the liver, and were sacrificed at postoperative day (POD) 1, 3, 5, and 7 with 8 rats in each time point for determination of the serum liver function parameters, and the mRNA and protein expression levels of TGF-β1 and Smad in liver tissue. The other 8 rats underwent sham operation for control. In addition, using the same modeling procedure, the influence of TGF-β/Smad pathway inhibitor (intraperitoneal injection of GW788388 before operation) on liver function and liver regeneration capacity in rats with liver fibrosis after partial hepatectomy.Results In rats in partial hepatectomy group compared with those in sham operation group, the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased on POD 1, and the gradually decreased with time (all P<0.05); the mRNA and protein levels of TGF-β and Smad in the liver tissue were significantly increased, both reached a peak on POD 3 (both P<0.05), and then decreased, and returned to the levels of rats in sham operation group on POD 7 (both P>0.05). In rats undergoing GW788388 injection before hepatectomy compared with those undergoing hepatectomy alone, the increasing amplitudes of AST and ALT were greater, and the expressions of cell proliferation mark Ki-67 and stem cell mark LGR5 were significantly reduced (all P<0.05).Conclusion The TGF-β/Smad signaling pathway plays an important role in terms of liver function protection and liver regeneration promotion in rats with liver fibrosis after partial hepatectomy. The possible mechanism may be associated with the regulatory effect in cell proliferation and stem cell differentiation of this pathway