OBJECTIVE To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid (ZNH) and rifampicin (RIF). METHODS Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF daily each for 28 d. For hepatoprotective studies, 0.25 g/kg per day of freshly prepared garlic homogenate was administered orally half an hour before the INH+RIF doses. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin were estimated on d 0, 14, 21, and 28 in all the rats. Histological analysis was carried out to assess the injury to the liver. Lipid peroxidation (LPO) as a marker of oxidative stress and non-protein thiols (glutathione) for antioxidant levels were measured in liver homogenate. RESULTS The treatment of rats with INH+RIF (50 mg/kg per day each) induced hepatotoxicity in all the treated animals as judged by elevated serum ALT, AST, and bilirubin levels, presence of focal hepatocytic necrosis (6/8) and portal triaditis (8/8). Garlic simultaneously administered at a dose of 0.25 g/kg per day prevented the induction of histopathological injuries in INH+RIF co-treated animals, except in 4 animals, which showed only moderate portal triaditis. The histological changes correlated with oxidative stress in INH+RIF treated animals. The group which received 0.25 g/kg per day garlic homogenate along with INH+RIF showed higher levels of glutathione (P<0.05) and low levels of LPO (P<0.05) as compared to INH+RIF treated group. CONCLUSIONS Freshly prepared garlic homogenate protects against INH+RIF-induced liver injury in experimental animal model.