Background & Objective: Hepatoprotective effect of antioxidants such as flavnoids has been demonstrated. The aim of the present study was to assess the hepatoprotective effect of the methanolic extract of Berberis integerrima fruit (MEBIF) on carbon-tetrachloride (CCL4) induced hepatotoxicity in rats. Materials & Methods: Forty male rats were divided into 5 groups as follows: 1) normal, 2) toxicant control (CCL4 was injected intraperitoneally (1 mg/kg bw), 3&4) toxicant rats treated with MEBIF at dose 250 and 500 mg/kg bw, and 5) toxicant rats treated with silymarin. At the end of the study, all the rats were sacrificed and some biochemical parameters of serum such as Alanine Aminotransferase (ALT), aspartate aminotransferase (AST) and Alk‌aline Phosphatase (ALP), total proptein, total bilirubin and albumin, and concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT) and FRAP (Ferric Reducing/Antioxidant Power) in liver tissue hemogenate were estimated. The Data was analyzed by one way variance analysis and Tukey’s test using SPSS 21. Results: injection of CCl4 significantly (P≤001/0) increased levels of ALT, AST, ALP, total bilirubin and MDA and decreased levels of total protein, albumin CAT, SOD (P≤ (001/0and FRAP in toxicant rats. In groups toxicant + Berberis (250&500) and toxicant + silymarin restored these changes to normal levels. Histopathological findings are cosistent with biochemical findings. Conclusion: MEBIF have a hepatoprotective effect on CCL4- induced hepatic damage in rats and these effects might be contributed to modulation of detoxification enzymes and antioxidant and free radical scavenger effects.