We investigated the effect of DL-alpha-lipoic acid (LA) supplementation and regular aerobic exercise on the concentrations of malondialdehyde (MDA) and vitamin E, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the levels of glutathione (GSH) in rat skeletal muscles (soleus and red gastrocnemius). For 8 weeks, rats (n = 7 per group) were (1) exercised on a treadmill for 30 min d(-1), (2) treated with supplemental LA, or (3) exercised and treated with supplemental LA. Control rats (n = 7) did not receive LA and were not exercised. DL-alpha-lipoic acid (100 mg kg(-1)) was administered daily as an oral supplement. The rats were exercised in a graded manner for 5 d wk(-1). The concentration of MDA in the soleus and red gastrocnemius was significantly lower in rats that exercised and received LA than in the other groups. Compared with the other groups, rats that exercised and received LA had a significantly higher vitamin E concentration in the soleus. The SOD and GPx activities in the soleus and red gastrocnemius were significantly higher in rats that exercised and received LA. These results suggest that LA supplementation combined with aerobic treadmill exercise inhibits lipid peroxidation in skeletal muscles. This effect was especially remarkable in the soleus, which is particularly sensitive to oxidative stress, as revealed by the increased vitamin E level and SOD and GPx activities.