Patients with Duchenne Muscular Dystrophy (DMD) experience ongoing muscle damage and inflammation, which reduces the muscle’s ability to regenerate. This results in chronically inflamed muscles that undergo progressive fibrofatty degeneration. Previously, we have shown that juvenile D2-mdx muscles exhibit altered inflammatory and myogenic responses that heighten disease severity as compared to juvenile B10-mdx and adult D2-mdx muscles. To better understand the changes that alter muscle repair in dystrophic muscles, we performed gene expression profiling of muscles in these mouse models from disease onset through adulthood. This identified a strong upregulation of pro-inflammatory chemokines and cytokines in juvenile D2-mdx mice, which affect immune cell signaling and recruitment in injured muscles. This aligns with the higher levels of neutrophils and macrophages seen in injured juvenile D2-mdx muscles. Interestingly, in adult D2-mdx mice, these immune pathways were less active, corresponding with their improved muscle repair. Based on these observations, we hypothesized that promoting resolution of inflammation and immune cell clearance from chronically injured muscles could help improve muscle regeneration in DMD. To test this, we used FPR2 receptor agonist drugs, which can help resolve inflammation by enhancing macrophage activity and promoting neutrophil degranulation. Administering these agonists before disease onset in juvenile D2-mdx mice reduced inflammation, prevented muscle degeneration, and improved muscle regeneration. In summary, our findings suggest that unresolved inflammation plays a key role in disease severity and progression in DMD, and identify pro-resolving therapies as a potential treatment to improve skeletal muscle health in DMD patients.