Oral administration of CCl4 at a dose of 1.2 g/kg body weight 3 times a week for 3 weeks significantly induced marked hepatic injury as revealed by increased activity of the serum enzymes ALT, AST, SALP and γ-GT. Methanolic extract of V. amygdalina administered 5 times a week for 2 weeks before CCl4 treatment at 250 and 500 mg/kg doses of the extract ameliorated the increase in the activities of these enzymes. Likewise the methanolic extract of V. amygdalina reduced the CCl4-induced increase in the concentrations of cholesterol, triglyceride and phospholipid by 37.8 % , 30.6 % and 8.5 % , respectively, and a reduction in the cholesterol/phospholipids ratio. These parameters were however increased at 750 mg/kg extract pretreatment. CCl4-induced lipid peroxidation was likewise attenuated by 57.2 % at 500 mg/kg dose of the methanolic extract of V. amygdalina. Similarly, administration of the extract increased the activities of the antioxidant enzymes: superoxide dismutase, glutathione S-transferase and reduced glutathione concentration significantly at 500 mg/kg (P<0.05) and catalase activity at 500–1000 mg/kg doses. These results suggest that methanolic extract of V. amygdalina leaves posseses protective effect against CCl4-induced hepatotoxicity by the antioxidant mechanism of action.