Skeletal muscle has high regenerative capability. It is able to regenerate completely after acute traumatic damage, while the repairing process often accompanied by fibrosis in the chronic degenerative conditions such as muscular dystrophy and repeated muscle fiber damage. Through in-depth study on the mechanisms of skeletal muscle fibrosis in the past decade, it has been found that a variety of cells and regulatory molecules involved in the process, especially muscle satellite cells-derived myofibroblasts, transforming growth factor β (TGF-β) and other fibrosis promoting growth factors. This review focused on the cellular and molecular mechanisms of the skeletal muscle fibrosis and relevant antagonistic strategies.