This experiment was carried out to investigate the role of antioxidants such as vitamin C and E, selenium and Nigella sativa (NS) on the prevention of carbon tetrachloride (CCl4)-induced liver fibrosis in rabbits. It was found that superoxide dismutase (SOD) values in ail of the treated groups were significantly lower than those of the control at 12(th) week of experiment (p < 0.05), while at 6(th) week and 12(th) week of experiment glutathione peroxidase (GSH-Px) values in the vitamin C treated group were significantly different from the control (p < 0.05). Histopathologically, hepatocellular necrosis, degeneration and advanced fibrosis were found in the control group. Lesions were minor and only confined to midzonal regions without centrilobular necrosis and fibrosis in the NS treated animals (group B). The lesions observed in the vitamin C treated animals (group C) were similar to that of the control group. Parenchymal changes with fibrosis were less in selenium and vitamin E treated animals (group D) than in those of the control group, but more obvious than in NS group. Histopathological findings demonstrate that NS might, at least partly, be successful in the prevention of liver fibrosis in rabbits. Vitamin E plus selenium had little therapeutic effect and vitamin C seemed to be ineffective, as far as the results of this study are concerned.