The objective of the study was to verify the effect of N-acetylcysteine (NAC) supplementation on parameters of oxidative damage and inflammatory response after high-intensity eccentric exercise (EE). 29 participants with a mean age of 21.3+/-4 yr, weight of 74.5+/-7.7 kg, and height of 177.2+/-6.9 cm were selected and divided randomly into 3 groups: placebo (21 days; n=8), NAC (21 days; n=9), and NAC plus placebo (14 days; n=8). Four participants withdrew from the study for personal reasons. 14 days after starting supplementation, the participants performed EE: 3 sets until exhaustion (elbow flexion and extension on the Scott bench, 80% 1RM). Blood samples were collected before and on the 2nd, 4th, and 7th day after EE. Muscle soreness (MS), lipoperoxidation, protein carbonylation, tumor-necrosis factor- (TNF-), and interleukin 10 (IL-10) were determined. Results showed a significant increase in MS in all the groups on the 2nd day after EE and a decrease in the following days. A significant increase was observed in malondialdehyde and carbonyl levels on the 4th and 7th days after EE in all groups. TNF- increased significantly on the 2nd day after eccentric exercise and decreased in the following days irrespective of NAC supplementation; concentration of IL-10 increased significantly on the 4th day in all groups. Only the supplemented groups maintained high levels of IL-10 on the 7th day after EE. The results suggest that treatment with NAC represents an important factor in the defense against muscle soreness and has different effects on oxidative damage and pro- and anti-inflammatory cytokines.