Spinal cord injury remains a devastating complication of thoracic and thoracoabdominal aortic operations. We aimed to investigate neuro-protective role of melatonin administered to rabbits before ischemia against ischemia-reperfusion (IR) injury. Occlusion of the abdominal aorta was applied to adult rabbits, followed by removal of aortic clamp and reperfusion. The abdominal aortas of New Zealand White albino rabbits (n = 18) were occluded for 30 minutes. Experimental groups were as follows: control group (sham operation group, n =10), Ischemia/reperfusion group (I/R) (n = 10) undergoing occlusion but receiving no pharmacologic intervention, Melatonin-treated group (n = 8) receiving 10mg/kg melatonin intravenously 10 minutes before ischemia. Neurologic status was assessed at 6, 24, and 48 hours after the operation. Spinal cords were harvested for histopathologic and biochemical analyses. Melatonin-treated animals had better neurologic function than those of the I/R group. Decreased tissue and serum malondialdehyde (MDA) levels and increased tissue and serum glutathione (GSH) levels were observed in melatonin-treated group (p<0.05). In the same group tissue and serum nitrate levels were decreased (p<0.05). Histopathologic analyses demonstrated typical morphologic changes characteristic of necrosis in I/R group. Melatonin attenuated ischemia-induced necrosis. Melatonin administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion. ©2008 Bentham Science Publishers Ltd.