It has been shown that phosphatidylcholine (PC) extracted from egg yolk possesses a variety of biological activities, such as anti-inflammatory and anti-oxidant effects, and prevents oxidative stress. The aim of this study was to evaluate the hepatoprotective effects of PC against carbon tetrachloride (CCl4), which is a well-known hepatotoxicant that causes extensive oxidative liver damage, and to investigate the mechanisms involved in this protective effect. Mice were treated with PC (0.1 ml, 10 or 100 mg/kg, orally) once daily for 5 consecutive days prior to CCl4 administration (0.1 ml, 20 mg/kg, intraperitoneally). The experimental data show that pretreatment with PC significantly prevented increases of serum aspartate transaminase, alanine transaminase, and alkaline phosphatase, and reduced reactive oxygen species levels. Histopathological evaluation of the liver also revealed that PC effectively ameliorated CCl4-induced hepatic injury and fibrosis. In addition, PC significantly counteracted the increase in glutathione levels and glutathione-S-transferase activity induced by CCl4. Concordantly, PC significantly decreased CCl4-induced upregulation of apoptotic proteins in the liver. These results suggest that PC exerts its protective effects against CCl4-induced hepatotoxicity via its activities as an anti-oxidant and free radical scavenger. (C) 2015 Elsevier Inc. All rights reserved.