BACKGROUND: Paraplegia due to ischemia/reperfusion (I/R) injury of the spinal cord is a devastating and undesired complication of thoraco-abdominal aortic surgery. Unidentified clots cause a variety of thromboembolic events and deteriorate the severity of ischemia. We investigated the effect of the degree of anticoagulation on spinal cord I/R injury and whether heparin is protective against I/R injury beside its anticoagulant properties. MATERIALS AND METHODS: Twenty-eight rats were randomly assigned to four groups (n=7 per group) as G1 (no aortic occlusion and heparin administration), G2 (45 min aortic occlusion; no heparin administration), G3 (45 min aortic occlusion; 400 IU/kg heparin to keep activated clotting time (ACT) level around 200 sec), and G4 (45 min aortic occlusion; 800 IU/kg heparin to keep ACT level around 600 sec). After neurologic evaluation at the 48th hour of reperfusion, lumbar spinal cords were removed for histopathologic evaluation and immunohistochemical staining for HSP70 (heat shock protein 70), interleukin-6 and myeloperoxidase (MPO). RESULTS: The Motor Deficit Index (MDI) scores were lowest in G1 group (p < 0.05) and the MDI scores of G3 and G4 were significantly lower than G2 group (p < 0.05).The neuronal degeneration in G3 was significantly lower than the other groups, respectively (p = 0.03). Histopathological evaluation showed no significant intergroup differences in terms of the degree of edema and inflammatory response. There was no statistically significant difference found among the groups in terms of HSP70 staining, IL-6 staining or the degree of MPO staining. CONCLUSIONS: Protection of spinal cord from I/R injury requires a multimodal management. We should not miss out the importance of adequate anticoagulation in thoraco-abdominal surgical procedures. Furthermore, the recently discovered anti-inflammatory property of glycosaminoglycans, including heparin, deserves to be investigated.