Skeletal muscle regeneration is a highly synchronized process involving the activation of various cellular and molecular events, coordinating inflammation and regeneration processes which are crucial for the beneficial outcome of tissue remodeling. Fibrosis, a failure of tissue remodeling, is initiated with muscle regeneration; however, it is the result of an excessive inflammatory response, representing an imbalance between enhanced production and deposition and impaired degradation of extracellular matrix (ECM) components of the muscle. Therefore, factors influencing the relative degree of muscle fiber regeneration as compared to the amount of scar formation have a critical role in functional muscle remodeling. Herein we have focused on the role of urokinase-type plasminogen activator (uPA) and transforming growth factor beta 1 (TGF/1) in ECM degradation and reconstitution in muscles.