Muscle injuries are challenging problems in traumatology and the most frequent injuries in sports medicine. Muscle injuries are capable of healing, although slowly and occasionally with incomplete functional recovery. We observed that lacerated muscle undergoes a rapid process of regeneration, which is hindered by the development of fibrosis. Biologic approaches to enhance muscle regeneration and prevent fibrosis are being investigated to improve muscle healing after injuries. We observed that growth factors can improve muscle regeneration but cannot prevent muscle fibrosis. We investigated the use of an antifibrosis substance, decorin, as an approach to prevent fibrosis and thereby improve muscle healing after injury in murine muscle. We observed that direct injection of human recombinant decorin can efficiently prevent fibrosis and enhance muscle regeneration in the lacerated muscle. More importantly, decorin can improve the recovery of strength in the injured muscle to a level similar to that observed in normal noninjured muscle. These results suggest that injection of decorin improves both the muscle structure and the function of the lacerated muscle to near complete recovery. This study will contribute significantly to the development of strategies to promote efficient muscle healing and complete functional recovery after muscle injuries.