OBJECTIVE There is increasing evidence that alcohol-induced liver damage may be associated with increased oxidative stress. We aimed to investigate free-radical scavenger effect of n-acetylcysteine in rats intragastrically fed with ethanol. METHODS Twenty-four rats divided into three groups were fed with ethanol (6 g/kg/day, Group 1), ethanol and n-acetylcysteine (1 g/kg, Group 2), or isocaloric dextrose (control group, Group 3) for 4 weeks. Then animals were sacrificed under ether anesthesia, intracardiac blood and liver tissues were obtained. Measurements were performed both in serum and in homogenized liver tissues. Malondialdehyde (MDA) level was measured by TBARS method. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were studied by commercial kits. Kruskal-Wallis test was used for statistical analysis. RESULTS ALT and AST in Group 1 (154 U/L and 302 U/L, respectively) were higher than those in Group 2 (94 U/L and 155 U/L) and Group 3 (99 U/L and 168 U/L) (P=0.001 for both). Serum and tissue levels of MDA in Group 1 (1.84 nmol/mL and 96 nmol/100 mg-protein) were higher than Group 2 (0.91 nmol/mL and 64 nmol/100 mg-protein) and Group 3 (0.94 nmol/mL and 49 nmol/100 mg-protein) (P<0.001 for both). On the other hand, serum GSH-Px level in Group 1 (8.21 U/g-Hb) was lower than Group 2 (16 U/g-Hb) and Group 3 (16 U/g-Hb) (P<0.001). Serum and liver tissue levels of SOD in Group 1 (11 U/mL and 26 U/100 mg-protein) were lower than Group 2 (18 U/mL and 60 U/100 mg-protein) and Group 3 (20 U/mL and 60 U/100 mg-protein) (P<0.001 for both). CONCLUSIONS This study demonstrated that ethanol-induced liver damage is associated with oxidative stress, and co-administration of n-acetylcysteine attenuates this damage effectively in rat model.