The purpose of this study was to investigate the effect of attenuation of exercise-induced oxidative stress by antioxidant administration on brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus. Wistar rats were assigned to four groups: non-exercise (Cont), exercise (Ex), or the combination of exercise with antioxidant administration (small dose: SP, large dose: LP) group. Exercise groups were subjected to treadmill running for 10 consecutive days. The exercise load increased gradually by 5 m/min per day for the first 5 days (10 m/min-30 m/min), and maintained at 30 m/min for the last 5 days. In addition, SP and LP were injected with N-tert butyl-a-phenyl nitrone (PBN) 1h prior to exercise. High-intensity exercise resulted in increased hippocampal 4-hydroxy-2-nonenal (4-HNE) contents compared with Cont. But this elevation was completely suppressed by a large dose of PBN. In Ex and SP, serum total antioxidative power were significantly decreased compared with Cont, whereas no changes were observed in LP. There was a significant negative correlation between hippocampal 4-HNE contents and serum total antioxidative power in SP and LP, suggesting the hypothesis that exercise-induced reduction in total antioxidant power might lead hippocampal 4-HNE accumulation. Furthermore, there was a significant increase of hippocampal BDNF level in LP compared with Cont and Ex. These findings indicate that an increase of oxidative stress might not have a beneficial effect on hippocampal BDNF expression. Our results of this study also suggest that attenuation of exercise-induced oxidative stress by some antioxidants contributes to BDNF expression in the hippocampus.