This sham-controlled animal study aimed to investigate the effects of melatonin and methylprednisolone combination on motor function, nerve conduction and histopathological and biochemical findings in rats with sciatic nerve crush injury. Forty-eight male Sprague-Dawley rats were divided into 6 groups (n = 8): CT: control, VEH: sciatic nerve injury, LMP: 15-mg/kg methylprednisolone, high-dose methylprednisolone (HMP): 30-mg/kg methylprednisolone, MEL: 15-mg/kg melatonin, MMP: 15-mg/kg methylprednisolone+15-mg/kg melatonin. The rats were evaluated with Sciatic Functional Index (SFI), nerve conduction study, interleukin-1β (IL-1ß), nerve growth factor (NGF), total antioxidant status (TAS), total oxidant status (TOS) and histopathological scores. There were no significant intergroup differences in baseline tests. SFI significantly improved in all treated groups with no significant intergroup differences. Motor amplitude improved most in MMP, LMP and MEL, respectively. Nerve conduction velocity significantly improved in MMP compared to VEH. There were no significant intergroup differences regarding serum NGF, TAS and TOS. Tissue NGF levels were higher in LMP, HMP and MEL. IL-1ß levels were significantly lower in CT and MMP. Tissue oxidative stress levels were significantly lower in treated groups compared to VEH, with no significant difference among them. MMP showed greater histopathological improvement. Melatonin combination therapy in sciatic nerve crush injury provided adequate functional improvement, superior electrophysiological and histopathological recovery compared to high-dose methylprednisolone and exhibited better anti-inflammatory activity through IL-1ß.