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Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate <jats:italic>mdx<\/jats:italic> mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre\u2010necrotic stage of muscular dystrophy as the relevant time frame for T\u2010cell\u2010based interventions. We focused on protein kinase C \u03b8 (PKC\u03b8, encoded by <jats:italic>Prkcq<\/jats:italic>), a critical regulator of effector T\u2010cell activation, as a potential target to inhibit T\u2010cell activity in dystrophic muscle. Lack of PKC\u03b8 not only reduced the frequency and number of infiltrating T cells but also led to quantitative and qualitative changes in the innate immune cell infiltrate in <jats:italic>mdx<\/jats:italic>\/<jats:italic>Prkcq<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> muscle. These changes were due to the inhibition of T cells, since PKC\u03b8 was necessary for T\u2010cell but not for myeloid cell infiltration of acutely injured muscle. Targeting T cells with a PKC\u03b8 inhibitor early in the disease process markedly diminished the size of the inflammatory cell infiltrate and resulted in reduced muscle damage. Moreover, diaphragm necrosis and fibrosis were also reduced following treatment. Overall, our findings identify the early T\u2010cell infiltrate as a therapeutic target and highlight the potential of PKC\u03b8 inhibition as a therapeutic approach to muscular dystrophy. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. 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