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Skeletal muscles of <jats:italic>mdx<\/jats:italic> dystrophic mice show distinct patterns of inflammation and regeneration, suggesting that factors within the microenvironment influence the adaptive responses of muscles with predominantly slow\u2010twitch or fast\u2010twitch fibers. This study aimed to verify the pattern of MMP activity in gastrocnemius, soleus, and diaphragm muscles and correlate it with the regenerative capability at distinct stages of the <jats:italic>mdx<\/jats:italic> myopathy. Marked inflammation and myonecrosis was associated with increased MMP\u20109 activity and TNF\u2010\u03b1 (tumor necrosis factor\u2010alpha) production, whereas muscle regeneration, evidenced by NCAM (neural cell adhesion molecule) expression and MMP\u20102 activity, varied at different stages of the disease. Soleus muscles showed a high percentage of NCAM\u2010positive myofibers in the early stages (2 weeks) of the disease, but they appeared in the gastrocnemius muscles at 12 weeks and in the diaphragm at 24 weeks. Increased MMP\u20102 activity in the diaphragm throughout all stages of the disease suggests important tissue remodeling, which is probably associated with persistent inflammation. The results indicate that the microenvironment of distinct skeletal muscle may influence a particular kinetic pattern of MMP activity, which ultimately favors persistent inflammation and myofiber regeneration at different stages of the myopathy in <jats:italic>mdx<\/jats:italic> mice. 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