Background: The functional restoration of skeletal muscle after injury is highly affected by its regenerative response that requires the coordinated regulation of inflammation, energy metabolism, and growth. Aim: The aim of the present study was to investigate the possible protective role of melatonin on cellular functions and tissue homeostasis during muscular regeneration after skeletal muscle injury in rats. Materials and Methods: The study was conducted on 80 male Wister rats with an open blunt injury of the left soleus muscle. Rats were divided into 2 groups; Group I (melatonin treated group), 40 rats with left soleus muscle injury and received intra peritoneal (i.p) injection of 10 mg/kg body weight/ day of melatonin. Group II (untreated group) 40 rats with soleus muscle injury and received equivalent volumes of 4.5% ethanol i.p. 3.3 mL/kg/day. Subsequent observations were performed at day 1, 4, 7, and 14 after injury, including muscle strength assessment, melatonin receptor Ia expression, bcl-2-associated-X protein (Bax) level and histological imaging. Results: Melatonin treatment significantly increased the twitch force of the injured muscle at day 1, 4, 7, and 14. MT1a receptor mRNA in the injured muscle showed a significant up-regulation in the melatonin treated group at day 4, 7 and 14. Intra peritoneal daily injection of melatonin for 4, 7, and 14 days resulted in significant decrease in Bax level in the injured soleus muscle in comparison to the corresponding injured muscles of untreated group. Histological examination further elucidated the anti-apoptotic and the anti-inflammatory action of melatonin. Conclusions: These data supported the hypothesis that melatonin supports muscle restoration after muscle injury, via its anti-inflammatory and anti apoptotic effects and thus might represent an attractive adjuvant therapy to optimize muscle healing after injury.