Objective to investigate the curative effect of activated vitamin D3 combined with IFN-α on CCl4-induced hepatic fibrosis in BALB/c mouse model. Methods the experimental mice received 100 μL of 10% CCl4 intraperitoneally to induce a model of hepatic fibrosis,and the nor-mal control group were administrated with same volume of 0.9% saline(n = 6). the experimental mice then were randomly divided into four treat-ment groups and treated for six weeks:saline therapy group(0.9% saline,100 μL/mouse,n = 6),IFN-α therapy group(IFN-α 800 U/mouse,n =6),1,25-(OH)2D3 therapy group(50 μg/kg,by gavaged,n = 6)and combined treatment therapy group(combined treatment,n=6). Hepatic inju-ry and hepatic pathology were examined by HE staining and Masson staining. Interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(tNF-α),transforming growth factor-β(tGF-β)and Smad3 were determined by real-time PCR and ELISA. Results Inflammatory cell infiltra-tion and periportal collagen deposition were significantly reduced in all the therapeutic group expect saline therapy group assessed by HE and Masson staining. the IFN-α therapy group,1,25-(OH)2D3 therapy group and combined treatment therapy group displayed significant decrease in Col1α1, IL-6,tNF-α,tGF-β and Smad3 expression and increase in IL-10 expression in liver tissue(P < 0.05). Conclusion the effect of 1,25-(OH)2D3 combined with IFN-α therapy is similar to separated treatment.