The process of tissue damage, repair, and regeneration in the skeletal muscle system involves complex inflammatory processes. Factors released in the inflammatory microenvironment can affect the phenotypic changes of macrophages, thereby changing the inflammatory process, making macrophages an important target for tissue repair treatment. Mesenchymal stem cells exert anti-inflammatory effects by regulating immune cells. In particular, exosomes secreted by mesenchymal stem cells have become a new cell-free treatment strategy due to their low tumorigenicity and immunogenicity. This article focuses on the mechanism of the effect of exosomes derived from mesenchymal stem cells on the phenotype of macrophages after skeletal muscle system injury and explores the possible mechanism of macrophages as potential therapeutic targets after tissue injury.