Hepatoprotective potential of methanolic extract of Clerodendrum infortunatum Linn. (MECI), which was widely used in Indian indigenous system of medicine, was studied against carbon tetrachloride induced hepatotoxicity in rats. Methanol extract at the dose of 100 and 200 mg/kg was administered daily along with carbon tetrachloride once in 72 hours for 14 days. The study was evaluated by assaying the serum biochemical parameters glutamate pyruvate transaminase (ALT), glutamate oxaloacetate transaminase (AST), alkaline phosphatase (ALP), bilirubin and total protein. Malondialdehyde (MDA) level, as well as reduced glutathione (GSH) content and catalase activity (CAT) was determined to explain the possible mechanism of the activity. The substantially elevated serum enzymatic levels of AST, ALT, ALP and total bilirubin were restored towards normalization significantly by the extract. Silymarin was used as standard reference and exhibited significant hepatoprotective activity against carbon tetrachloride induced haptotoxicity in rats. MDA concentration was decreased, while the liver antioxidative enzyme activity was elevated in all the MECI treated rats. All the results were compared with standard drug silymarin. In addition, histopathology of liver tissue was investigated to observe the morphological changes, showed the reduction of fatty degeneration and liver necrosis. The results of this study revealed that methanol extract of C. infortunatum has moderate hepatoprotective activity. This effect may be due to the ability of the extract to inhibit lipid peroxidation and increase in the anti-oxidant enzymatic activity.