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Although the intake of nonsteroidal anti-inflammatory drugs ( NSAIDs) intake by athletes prevents soreness, little is known concerning their role in exercise performance. This study assessed the effects of ibuprofen intake on an exhaustive protocol test after 6 weeks of swimming training in rats. Animals were divided into sedentary and training groups. After training, animals were subdivided into two subsets: saline or ibuprofen. Afterwards, three repeated swimming bouts were performed by the groups. Ibuprofen (15 mg/kg) was administered once a day. Pain measurements were performed and inflammatory and oxidative stress parameters were assayed in cerebral cortex and gastrocnemius muscle. Training, ibuprofen administration, or both combined ( P < 0.05; 211 ± 18s, 200 ± 31s, and 279 ± 23s) increased exercise time to exhaustion. Training decreased the acetylcholinesterase ( AChE) activity ( P < 0.05; 149 ± 11) in cerebral cortex. Ibuprofen intake decreased the AChE activity after exhaustive protocol test in trained and sedentary rats ( P < 0.05; 270 ± 60; 171 ± 38; and 273 ± 29). It also prevented neuronal tumor necrosis factor-α ( TNF-α) and interleukin ( IL 1β) increase. Fatigue elicited by this exhaustive protocol may involve disturbances of the central nervous system. Additive anti-inflammatory effects of exercise and ibuprofen intake support the hypothesis that this combination may constitute a more effective approach. In addition, ergogenic aids may be a useful means to prevent exercise-induced fatigue. [ABSTRACT FROM AUTHOR]