α-Lipoic acid (αLA), as an inductor of hydrogen peroxide (H2O2) and nitrogen oxide (NO) generation and modulator of thiol redox status, plays an important role in cell signalling pathways. The study was designed to observe the effect of αLA on inflammatory response through changes in H2O2 and NO levels as well as thiol redox status. Sixteen physically active males were randomly assigned to one of two groups: placebo or αLA (1,200 mg d(-1) for 10 days prior to exercise). The exercise trial involved a 90-min run at 65% VO2max (0% gradient) followed by 15-min eccentric phase at 65% VO2max (-10% gradient). Blood samples were collected before the exercise trial and then again 20 min, 24, and 48 h after. αLA significantly elevated H2O2 but reduced NO generation before or after exercise. Thiol redox status (GSHtotal-2GSSG/GSSG) increased by >50% after αLA and exercise (ANOVA, P < 0.05) and correlated with changes in cytokines interleukin-6 (IL-6) (r = -0.478, P < 0.05) and IL-10 (r = -0.455, P < 0.05). This was caused by strong effect of αLA on GSSG concentration. αLA elevated IL-6 and IL-10 levels at 20 min after exercise and decreased in interleukin-1β and tumor necrosis factor α before and after exercise. This enhanced the regeneration of injured muscles. Creatine kinase activity tended to lower values after αLA intake. The study suggests that the combination of intense exercise with α-lipoic acid intake might be useful to improve the skeletal muscle regeneration through changes in inflammatory response which are associated with H2O2 and NO generation as well as thiol redox status.