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To investigate the hepatoprotective and antioxidant effects of ethanol extract of Enicostemma littorale Blume (Ens) against CCl4 induced hepatic injury in albino rats. Male albino rats of six numbers in each group were undertaken for study. Hepatoprotective and antioxidant effect of E. littorale Blume (Ens) ethanol extract at a dosage of 100 & 200 mg/kg body weight was evaluated. The degree of hepatoprotection was assessed by measuring the activity levels of the marker enzymes such as serum aspartate transaminase (AST), alanine transaminase (ALT) alkaline phosphatase (ALP), acid phosphatase (ACP) and total bilirubin. Lipid peroxidation caused by free radicals was assessed by measuring the activity levels of the tissue antioxidant enzymes such as glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD). The CCl4 administered rats recorded elevated activity levels of serum AST, ALT, ALP and ACP revealing CCl4 induced hepatotoxicity. In the groups treated with 100 mg/kg and 200 mg/kg of the extract, the above biochemical markers of hepatotoxicity were found to be decreased when compared to CCl4 treated control group. Both the doses of ethanol extract of Enicostemma littorale (EEEL) used in the study showed significant protective property than the control. In the groups treated with 100 mg/kg and 200 mg/kg of the extract, GPX, SOD and catalase were found to be increased when compared to CCl4 treated control group. It can be concluded that the ethanol extract of E. littorale Blume is not only hepatoprotective but also possess significant antioxidant property.