Ethanol extract of Clausena dentata (Willd.) M. Roem (Rutaceae) was evaluated for hepatoprotective activity in rats. The plant extract (250 mg/kg, p.o.) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity as judged from the serum markers for liver damage. Acetaminophen induced a significant rise in aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP) and decrease in total protein. Treatment of rats with ethanol extract (250 mg/kg) significantly (P<0.001) altered serum marker enzymes levels to near normal against acetaminophen treated rats. The activity of the extract was comparable to the standard drug, silymarin (50 mg/kg, p.o.). Histopathological changes of liver sample were compared with respective control. Results indicate that Clausena dentata possesses hepatoprotective effect on acetaminophen-induced hepatotoxicity in rats.