In this study, we report protective effects of dietary l-arginine (l-Arg) supplementation against oxidative stress and inflammation in aging rats during exhaustive exercise. Thirty 18-month-old male Sprague–Dawley rats were randomly divided into four groups: sedentary control (SC); sedentary control with l-Arg treatment (SC + Arg); exhaustive exercise (E); and exhaustive exercise with l-Arg treatment (E + Arg). Rats in groups SC + Arg and E + Arg received a 2% l-Arg diet. Rats in groups E and E + Arg performed an exhaustive running test on a treadmill. The mean duration of exercise differed significantly between groups E and E + Arg (51 ± 6 versus 63 ± 3 min). Results showed significant increases in xanthine oxidase (XO) and myeloperoxidase (MPO) activities and in lipid peroxidation end-product (malondialdehyde, MDA) levels of myocardial, muscular, hepatic, pulmonary, and renal tissues of exercised rats compared with SC and SC + Arg rats. The increased XO and MPO activities and MDA levels significantly decreased in exercised rats that were fed a diet supplemented with l-Arg. We also found that l-Arg supplementation prevented exhaustive exercise-induced elevations of plasma aminotransferase activity, and lactate and uric acid levels in aging rats. These findings suggest that l-Arg supplementation enhances exercise capacity and protects against oxidative damage and inflammatory responses caused by exhaustive exercise in aging rats.