This study investigated the protective effects of ethyl pyruvate (EP) against carbon tetrachloride (CCl4)-induced acute hepatic injury in rats. The administration of a single dose of CCl4 (1.6 g/kg body weight) significantly elevated the levels of malondialdehyde, nitric oxide, alanine transaminase, aspartate transaminase, and alkaline phosphatase, cholesterol, low-density lipoprotein cholesterol, and triglycerides. In addition, CCl4 was found to significantly suppress the activity of superoxide dismutase, catalase, and glutathione peroxidase. All of these parameters were restored to their normal levels by the administration of EP before and after the CCl4 injection. Moreover, the number of positive apoptotic hepatocytes had significantly increased in the CCl4 group but decreased in rats treated with EP along with CCl4. Histopathological changes induced by CCl4 were also ameliorated by EP treatment. These findings provided evidence that EP, because of its antioxidant and anti-apoptotic action, could protect rat liver against CCl4-induced acute liver injury.