ABSTRACT Objective:To evaluate the hepatoprotective potential of ethanolic (50%) extract ofZiziphus oenoplia (L.) Mill (Z. oenoplia) root against isoniazid(INH) and rifampicin(RIF) induced liver damage in animal models.Methods: Five groups of six rats each were selected for the study. Ethanolic extract at a dose of 150 and300 mg/kg as well as silymarin (100 mg/kg) were administered orally once daily for21d in INH + RIF treated groups. The serum levels of glutamic oxaloacetic transaminase(SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), and bilirubin were estimated along with activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione peroxidase, and hepatic melondialdehyde formation. Histopathological analysis was carried out to assess injury to the liver.Result: The considerably elevated serum enzymatic activities of glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin due toINH + RIF treatment were restored towards normal in a dose dependent manner after the treatment with ethanolic extract of Z. oenopliaroots. Meanwhile, the decreased activities of superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were also restored towards normal dose dependently. In addition, ethanolic extract also significantly prevented the elevation of hepatic melondialdehyde formation in the liver ofINH + RIF intoxicated rats in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver sections.Conclusions: The results of this study strongly indicate that ethanolic extract of Z. oenoplia has a potent hepatoprotective action againstINH + RIF induced hepatic damage in rats.