AIM: To investigate the effect of interferon-alpha (IFN-alpha) on preventing or reversing hepatic fibrosis in rat experimental model induced by CCl4. METHODS: One hundred and ten Sprague-Dawley rats were divided into five groups: group A (normal controls, n = 18), group B (fibrotic model controls, n = 22), group C (IFN-alpha prevention, n = 22) initially treated with intramuscular injection of IFN-alpha in saline daily at the doses of 1x105 U for 6 wk, group D (IFN-alpha treatment, n = 24) treated with intra-muscular injection of IFN-alpha in saline daily at the doses of 1x105 U for 6 wk after the first 6 wk, group E (0.9% sodium chloride treatment control, n = 24) treated with intra-muscular injection of 0.01 mL/kg daily for 6 wk after the first 6 wk. At the end of the experiment, all rats of each group were killed. Samples of the liver obtained by biopsy were subjected to histological, immunohistochemical and electron microscopic studies for the expressions of transforming growth factor-beta 1 (TGF-beta 1) and alpha-smooth muscle actin (alpha-SMA). RESULTS: The expressions of TGF-beta 1, the number of activated hepatic stellate cells and alpha-SMA in hepatic tissue of group C were significantly less than those of group B (P<0.01). The degree of fibrosis score in group B was also significantly less than that of group C under light microscope (P<0.01). CONCLUSION: IFN-alpha can inhibit the production of TGF-beta 1, decrease HSC activation and stimulate its apoptosis. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.