The lack of dystrophin in mdx mice, an animal model for Duchenne muscular dystrophy, leads to cycles of muscle degeneration and regeneration processes. The aim of this study was to examine how low-intensity endurance exercise affects the regeneration process in dystrophin-deficient skeletal muscle. Male adult mdx (C57BL/10ScSn-Dmd^mdx/J; 10-wk old) and wild type mice were subjected to low-intensity endurance exercise by running on a motorized Rota-Rod for 5 days/week for 4 weeks at progressively increasing loads. Histomorphological analysis showed a significant reduction of both muscle necrosis foci and regeneration processes in the gastrocnemius and quadriceps muscles of exercised mdx mice. The reduction of regeneration process was also evaluated by examining the protein expression of connexin-39 (Cx39), a specific gene involved in the regeneration process of injured muscles. While Cx39 was not expressed both in wild type exercised nor in sedentary mice, it was markedly increased in sedentary mdx mice, because of active degeneration/regenerating process, and dropped to very low levels in exercised mdx mice, suggesting a reduction of muscle regeneration process. Exercised mdx mice showed a trend to lower body weight gain and positive effect on the degree of fatigue. The results of this study provide evidence for beneficial effects of low-intensity endurance exercise in regenerating muscle of mdx mice, leading to recovery of damaged muscle and to muscle function improvement.