Abstract: Carbon tetrachloride (CCl4) is a known chemical with high incidence hepatotoxicity. The objective of this study was to investigate the acute toxicity and hepatoprotective activity of methanol extract of root of Tephrosia calophylla against CCl4 induced hepatotoxicity. Animals were pretreated with the methanol extract of Tephrosia calophylla (150 and 300 mg kg-1 b.wt.) for 14 days and then challenged with CCl4 (1.5 mL kg-1 b.wt.) in olive oil (1:1, v/v) on 14th day. Serum marker enzymes (ALP, SGOT, SGPT, total protein, albumin and total bilirubin) were estimated in all the study groups. For acute toxicity study it was found that the LD50 value of methanol extract of Tephrosia calophylla was 1000 mg. The results of biochemical parameters revealed the elevation of biochemical markers like SGPT, SGOT, ALP and bilirubin in toxicant treated group indicating that CCl4 induces damage to the liver. Pretreatment with methanolic extract of Tephrosia calophylla significantly reduced the elevated levels of SGPT, ALP and Bilirubin, but not SGOT. Low level of total protein and albumin in toxicant treated group and the significant elevation in methanolic extract of Tephrosia calophylla treated group shows protection of against in CCl4 induced liver injury. The extract of Tephrosia calophylla treated rats when compared with standard Liv 52 group and extract control group there was no significant different in biochemical parameters.