Purpose: This study aimed to evaluate whether supplementation with L-arginine alone or in combination with physical exercise training can modulate rats' lipid and inflammatory profiles after a single intense exercise session. Methods: Male Wistar rats were divided into four different groups: control (C), trained (T), supplemented with L-arginine (C + A) and trained and supplemented (T + A). Animals from supplemented groups (C + A and T + A groups) received 300 mg/kg animal body weight L-arginine diluted in 30 mL of drinking water for 8 weeks. Exercise training protocol (moderate intensity--70% achieved in the maximum effort test) was held 5 days/week for 8 weeks. Results: Exercise training induced a decrease in the amount of plasma, cholesterol and triglyceride totals, and skeletal muscle VEGF and CINC. Supplementation alone showed a benefit by reducing LDL levels. Conclusion: Training combined with supplementation showed a pronounced reduction in skeletal muscle VEGF and CINC amount. L-arginine supplementation, especially when associated with the regular aerobic physical exercise at moderate intensity was able to improve not only plasma lipid profile but also the inflammatory response of skeletal muscle immediately after an exhaustive physical exercise session.