Many hepatoprotective herbal preparations have been recommended in alternative systems of medicine for the treatment of hepatic disorders. No systematic study has been done on protective efficacy of Capparis spinosa (Capparidaceae) to treat hepatic diseases. Protective action of C. spinosa ethanolic root bark extract was evaluated in this study in an animal model of hepatotoxicity, which was induced by carbon tetrachloride.Healthy male mice (30-35 g body weight, 6-8 week old) were divided into 7 groups. Group 1 was normal control group; Group 2, the hepatotoxic group was given CCl4; Group 3 was administered olive oil (vehicle); Groups 4-6 received different doses of ethanolic root bark extract (100, 200 & 400 mg/kg) with CCl4; Group 7 was administered overdose of the extract (800 mg/kg). The parameters studied were alanine transaminase and aspartate transaminase activities and duration of sleep. The hepatoprotective activity was also supported by histopathological studies of liver tissue.Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum enzyme activities, reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with ethanolic root bark extracts showed significant decrease in the levels of serum markers, indicating the protection of hepatic cells. The results revealed that ethanolic root bark extract of C. spinosa could afford significant dose-dependent protection against CCl4 induced hepatocellular injury.