Background Acute muscle injury has been recognized as a global healthcare issue. obestatin derived from a polypeptide called preproghrelin and involved in muscle regeneration. Microvesicles (MVs) exist in almost all types of body fluid. Aim of the work To evaluate the regenerative and myogenic capabilities of both obestatin and adipose stem cell derived microvesicles in repairing rats skeletal muscle injury. Material and Methods Sixty-five adult male rats were divided into five groups. Group I: control group. Group II: twenty rats undergo thermal muscle injury, then subdivided into two subgroups; IIa & IIb. Group ΙIΙ (Obestatin): rats received injections of obestatin (30 μg/Kg) into tibialis anterior muscle each 24 hours for five days one week after muscle injury. Group ΙV (MVS): rats received a single dose of 15μg MVs into tibialis anterior muscle one week after muscle injury. Group V (Obestatin and MVS): rats received obestatin and MVs together (as in groups III & IV). Rats were sacrificed after four weeks after thermal injury (only group IIa sacrificed after one week) and specimens processed and examined using histological and immunohistochemical techniques. Results Group II (a & b) showed nearly the same histological picture of severe muscle disruption but there was a significant increase in collagen fibers deposition (P˂ 0.01) in groups IIb compared with group IIa. Group III and IV showed improvement in histological picture compared with group II. Group V showed a histological picture nearly similar to control group. Conclusion: Obestatin and Microvesicles (MVs) enhanced the repair of muscle injury. The effect of obestatin and microvesicles together is better than their use separately.