Rats and primary cultures of rat hepatocytes were used as the in vivo and in vitro models to evaluate the hepatoprotective activity of sub-fractions from total methanol extract of Baliospermum montanum. Carbon tetrachloride was selected as hepatotoxin. Silymarin was the reference hepatoprotective agent. In the in vivo study, serum transaminases, alkaline phosphatase, total bilirubin, total cholesterol, albumin together with total protein and histopathological examination were the criteria for the evidences of liver injury. Carbon tetrachloride caused the alterations in all the biochemical parameters and centrilobular necrosis. Among the Ethyl methyl ketone and methanol sub-fractions tested (50, 100 and 150 mg/kg), methanol sub-fraction (150 mg/kg) of the bio-active total methanol extract and silymarin (100 mg/kg) enhanced liver cell recovery by restoring all the altered biochemical parameters back to normal. In the in vitro study, release of transaminases, total protein together and hepatocyte viability were the criteria. Primary cultures of hepatocytes were treated with carbon tetra chloride (10 μl/ml), and various concentrations (100, 500 and 1000 μg/ml) of ethyl methyl ketone and methanol sub-fractions of total methanol extract and silymarin (100 μg/ml). Carbon tetrachloride reduced the hepatocyte viability and also altered the biochemical parameters, which were restored significantly (P<0.05) by ethyl methyl ketone (1000 μg/ml) and methanol (500 and 1000 μg/ml) sub-fractions. These results suggest that Baliospermum montanum possess the hepatoprotective activity against carbon tetrachloride induced liver injury in both rats and primary cultures of rat hepatocytes.