This preliminary research determines whether a combination of reverse end-to-side neurorrhaphy and rapamycin treatment achieves a better functional outcome than a single application after prolonged peripheral nerve injury. We found that the tibial nerve function of the reverse end-to-side + rapamycin group recovered better, with a higher tibial function index value, higher amplitude recovery rate, and shorter latency delay rate (P 0.05). The reverse end-to-side + rapamycin group better protected the gastrocnemius muscle with more forceful contractility, tetanic tension, and a higher myofibril cross-sectional area (P 0.05). Combining reverse end-to-side neurorrhaphy with rapamycin treatment is a practical approach to promoting the recovery of chronically denervated muscle atrophy after peripheral nerve injury.