Dietary cholesterol is suggested to cause atherosclerosis and to increase the production of free radicals. It is reported that hypercholesterolemic diet may make some changes on the antioxidant system. In our study, we aimed to observe the effect of N-acetylcysteine (NAC) treatment on the oxidative stress that is caused by hypercholesterolemia.53 female Sprague-Dawley rats were placed into 5 different groups randomly, as control, cholesterol, NAC1, NAC2and NAC3. The control group was fed with standard basal rat chow while the others were fed with basal chow enriched with 1% cholesterol for 8 weeks. NAC was also administered to the treatment groups intraperitoneally (25, 50 or 100 mg/kg/day of doses). At the end of the study, malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), cholesterol and trigliseride were analyzed in the blood and tissue samples. The results were analyzed by Kruskal Wallis variance analysis and then by Mann-Whitney U test.While the whole blood GSH levels in the cholesterol group were decreased, the plasma levels of cholesterol, MDA and NO were elevated. In the NAC1treatment group with 25 mg/kg/day dose, liver tissue MDA levels were higher than those of the cholesterol group. In the NAC2treatment group with 50 mg/kg/day dose, tissue and plasma MDA levels were decreased in comparison with the cholesterol group. On the other hand, tissue nad plasma MDA levels were significantly increased in the NAC3group, receiveing 100 mg/kg/day dose.In the light of our findings, we can tell that hypercholesterolemic diet causes oxidant stress and an imbalance on antioxidant defense systems. To avoid the oxidative impairment caused by hypercholesterolemia, 25 mg/kg/day NAC dose is not enough, 100 mg/kg/day NAC dose shows toxic effects. We conclude that the most effective dose is 50 mg/kg/day.