Objectives: To evaluate the effects of intravenous methylene blue (MB) administration on ischemia-reperfusion (I/R) injury of the spinal cord (SC). Methods: 16 rabbits were randomly assigned either to group M (n = 8; receiving MB, intervention group) or group C (n = 8; control group) and underwent a 30-min period of SC ischemia by clamping the abdominal aorta between the left renal artery and the aortic bifurcation. 15 min before clamping, rabbits received either intravenous MB (10 mg/kg; group M) or normal saline (group C). The two groups were compared 24 h postoperatively both histologically and for neurological function, using a Tarlov score. Measurements to determine levels of malondialdehyde (MDA) and glutathione (GSH) in the SC tissue were also performed. Results: Neurological impairment and spinal tissue MDA levels were significantly lower in animals treated with MB (p < 0.001). In contrast, spinal GSH levels were significantly higher in group M (p < 0.001). Histological examination revealed that the integrity of the SC was better preserved in the MB group, whereas cords from the control group exhibited evidence of acute neuronal injury. Conclusions: The prophylactic use of MB reduces neurological injury and improves clinical outcomes in the rabbit SC I/R model. These effects are probably mediated by the drug's antioxidant properties. Copyright (c) 2006 S. Karger AG, Basel.