OBJECTIVE Prove the attenuated effects of N-acetylcysteine (NAC) on oxidative stress in rats with nonalcoholic steatohepatitis (NASH). METHODS Male Sprague-Dawley rats were randomly divided into five groups. Group I (normal control) was fed regular dry rat chow (RC) for 6 weeks. Group 2 (NASH) was fed 100% fat diet for 6 weeks. Group 3-5 were fed 100% fat diet for 6 weeks, and then switched to RC alone (NASH + diet ; group 3), to RC + 20 mg/kg/day of NAC orally (NASH + diet + NAC20; group 4) or to RC + 500 mg/kg/day of NAC orally (NASH + diet + NAC500; group 5) for 4 weeks, respectively. They were sacrificed to collect blood and liver samples at the end of the present study. RESULTS Levels of total glutathione (GSH), serum cholesterol, and hepatic malondialdehyde (MDA) were increased significantly in the NASH group compared with normal control. Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation. Treatment with diet or diet plus NAC reduced the levels of GSH, cholesterol, and hepatic MDA back to normal. Liver sections from group 3-5 showed a decrease in fat deposition and necroinflammation in hepatocytes. However, no differences on all variables existed between diet alone and diet plus NAC groups. CONCLUSIONS Our data indicate that diet or diet plus NAC treatment could attenuate oxidative stress and improve liver histopathology of NASH. However the addition of NAC is not better than diet treatment alone.