Carbon tetrachloride (CCl(4)) is a well-known model for inducing chemical hepatic injury in Swiss albino mice. The present study was designed to examine the ability of lycorine a natural alkaloid compound to prevent CCl(4)-induced hepatotoxicity in the Swiss albino mice. After the experimental period of 8 weeks, CCl(4) significantly increased the generation of lipid peroxidation products, it reflected by high levels of malondialdehyde, hepatic marker enzymes like aspartate transaminase, Alanine transaminase, Lactate dehydrogenase, alkaline phosphatase and lipids profiles. These increases were accompanied by significant decreases of glutathione (GSH); vitamin C content and significant reduction in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and GSH reductase were observed in the mice liver, which were normalized by the lycorine treatment as compared with CCl(4)-induced group of mice. Moreover, the histological and ultrastructural observations evidenced that lycorine effectively rescues the hepatocyte from CCl(4)-induced oxidative damage without disturbing its cellular metabolic function and structural integrity. Therefore, lycorine may be considered a potent antioxidant against free radical-related diseases.