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Objective: Radiation myelopathy (RM) is known as a serious complication of head andneck radiation therapy. Furthermore, the radioprotective roles of melatonin have beeninvestigated on different tissues. The aim of this study was to assess the radio protectiveeffects of melatonin on biochemical, histopathological and clinical manifestations of RMin the rat cervical spinal cord.Materials and Methods: Four groups of rats were investigated as follows: The controlgroup was treated with vehicle. The second group (melatonin only) was intraperitoneallyinjected with 100 mg/kg melatonin. The third group's (radiation) cervical spinal cord areawas irradiated with 22 Gy cobalt-60 gamma-rays. The fourth group (melatonin plus irradiation)received 100 mg/kg melatonin intraperitoneally, and after 30 minutes their spinalcord area was irradiated with 22 Gy gamma radiation. Five animals from each group wererandomly 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 controlgroup (p<0.001). Furthermore, the GSH levels in this group were significantly lowerthan that of those in the control group (p<0.001). Administration of melatonin markedlyreduced MDA (p<0.001) and increased GSH (p<0.05) levels in this group. Demyelinationand clinical signs of myelopathy were decreased in the melatonin plus irradiation group incomparison to the irradiated group.Conclusion: Our study confirms the radioprotective effects of melatonin at early stagesof biochemical, as well as late histological and clinical changes in the spinal cord.