Abstract: Background and Objective: The stem bark of Commiphora kerstingii Engl. is used in northern Nigeria to treat jaundice and other liver diseases. In this study, C. kerstingii stem bark extract was investigated for its effect in acute liver injury induced by carbon tetrachloride (CCl4). Materials and Methods: A limit test was employed to determine acute toxicity and median lethal dose. To determine its effect in acute liver injury, rats were pre-treated with C. kerstingii extract (50, 100, 200 mg kg–1), distilled water (5 mL kg–1) or silymarin (100 mg kg–1), 1 hr before intraperitoneal injection of carbon tetrachloride and repeated once daily for 5 days. After 5-day pre-treatment and challenge, the liver and serum biochemical parameters were assessed. Liver tissue homogenate was assayed for antioxidant effect. Results: The extract was not acutely toxic and produced no mortality. Relative liver weight, alanine aminotransferase, total bilirubin changes in 200 mg kg–1 extract-treated groups were insignificant (p>0.05) relative to the unchallenged control group. Pathological changes observed in the CCl4-challenged control group was mitigated in 200 mg kg–1 extract-treated groups. The liver homogenate of extract-treated groups showed an increase in antioxidant capacity relative to the normal and CCl4-challenged control groups. In all the parameters studied, the effects of the extract were comparable to those produced by silymarin. Conclusion: Commiphora kerstingii stem bark extract is acutely safe when administered orally and possesses protective effects against acute liver injury, likely mediated by its ability to restore antioxidant defense.