Objective: Radiation myelopathy (RM) is known as a serious complication of head and neck radiation therapy. Furthermore, the radioprotective roles of melatonin have been investigated on different tissues. The aim of this study was to assess the radio protective effects of melatonin on biochemical, histopathological and clinical manifestations of RM in the rat cervical spinal cord. Materials and Methods: Four groups of rats were investigated as follows: The control group was treated with vehicle. The second group (melatonin only) was intraperitoneally injected with 100 mg/kg melatonin. The third group's (radiation) cervical spinal cord area was irradiated with 22 Gy cobalt-60 gamma-rays. The fourth group (melatonin plus irradiation) received 100 mg/kg melatonin intra peritoneally, and after 30 minutes their spinal cord area was irradiated with 22 Gy gamma radiation. Five animals from each group were randomly selected. 72 hours, 8 and 22 weeks after irradiation for analysis of malondialdehyde (MDA) and glutathione (GSH) levels, and underwent histopathological studies. Results: The MDA levels in the irradiation group were significantly higher than in the control group (p<0.001). Furthermore, the GSH levels in this group were significantly lower than that of those in the control group (p<0.001). Administration of melatonin markedly reduced MDA (p<0.001) and increased GSH (p<0.05) levels in this group. Demyelination and clinical signs of myelopathy were decreased in the melatonin plus irradiation group in comparison to the irradiated group. Conclusion: Our study confirms the radioprotective effects of melatonin at early stages of biochemical, as well as late histological and clinical changes in the spinal cord.