Objective. Short term exhausting exercise increases the formation of harmful reactive oxygen species. We evaluated effect of vitamin E supplementation prior to swimming on circulating inflammatory markers, muscle endothelial nitric oxide synthase (eNOS) expression, functional and structural changes of muscle and kidney of rats. Methods. 24 male albino rats were divided into 3 groups: (C) control group (not submitted to exercise stress), (S) exercise stress group, and (SE) exercise stress and vitamin E group. The rats from SE group were treated with gavage administration of vitamin E (50 mg·kg⁻¹) prior to swimming. The animals from S and SE groups were submitted to bouts of swimming exercise stress for 1 hour daily for a week. Results. We found that swimming stress significantly elevated plasma tumor necrosis factor-alpha (TNF-α), interferon gamma (INF-γ) and C reactive protein (CRP). Exercise stress caused significant decrease in relative kidney weight, Total body weight (TBW), plasma urea and creatinine levels 30 min. after the last session of exercise. However, it significantly increased urea to creatinine ratio and caused considerable damage in kidney cells as revealed by histological examinations. Microscopic examination of muscle samples showed hypervascularity, raised nuclear number, splitting of muscle fibers, and central location of nuclei. Administration of vitamin E for seven consecutive days before the exposure to exercise significantly decreased TNF-alpha, INF-gamma and didn't change CRP level. Vitamin E supplementation decreased urea to creatinine ratio, increased TBW, increased endothelial nitric oxide synthase (eNOS) expression and ameliorated the structural changes that occurred in the muscle and kidney. Conclusion. Present study revealed that vitamin E supplementation has promising protective role against exercise-induced elevation of cytokines, muscular damage as well as dehydration and potential renal damage