This study investigated the protective effects of ethyl pyruvate (EP) against carbon tetrachloride (CCl)-induced acute hepatic injury in rats. The administration of a single dose of CCl (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, CCl 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 CCl injection. Moreover, the number of positive apoptotic hepatocytes had significantly increased in the CCl group but decreased in rats treated with EP along with CCl. Histopathological changes induced by CCl 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 CCl-induced acute liver injury.