Herbal medicines derived from plant extracts are being increasingly utilized to treat a wide variety of clinical diseases. In the present study, the hepatoprotective activity of methanolic extract of the fruits of Solena amplexicaulis (Family, Cucurbitaceae) at doses of 250 mg/kg and 500 mg/kg body weight per oral were evaluated by carbon tetrachloride intoxication in rats. The toxic group which received Carbon tetrachloride (1ml/kg body weight per oral.) dissolved in 1:1 ratio in olive oil alone exhibited significant increase in serum alanine amino transferase, aspartate amino transferase, alkaline phosphatase and total bilirubin levels compared to the groups received pretreatment of Solena amplexicaulis per oral. The extract treated group remarkably controlled the aspartate amino transferase, serum alanine amino transferase, alkaline phosphatase and total bilirubin levels in serum and the effects were comparable with standard drug (silymarin 100 mg/kg body weight per oral). The histological examinations of the liver showed propound steatosis degeneration and nodule formation in the hepatic architecture of carbon tetrachloride treated rats. But the animals received pretreatment of the extract shown decreased necrotic zone and hepatocellular degeneration when compared to the liver exposed to carbon tetrachloride intoxication alone. This study suggests that methanolic extract of the fruit of Solena amplexicaulis has a liver protective effect against carbon tetrachloride-induced hepatotoxicity.