Spinal cord injury (SCI) is a serious condition that produces life-long disabilities. Only limited therapeutic measures are currently available for its treatment. This review describes the role of leukocytes in pathologic mechanisms of trauma-induced SCI in rats, which contributes to new understanding of the pathologic process involved in SCI and could lead to the development of new therapeutic strategies by which leukocyte activation can be regulated. SCI induced by trauma is a consequence of an initial physical insult that is followed by a progressive injury process which involves various pathochemical events that lead to tissue destruction. Therapeutic intervention in SCI should therefore be directed at reducing or alleviating this secondary process. Although the mechanisms are not fully understood, progressive vascular events, especially activated neutrophil-induced endothelial cell damage, have been shown to be implicated. We have found that some therapeutic agents, which inhibit leukocyte activation directly or indirectly, alleviate the motor disturbances observed in a rat model of SCI. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two pharmacological agents currently clinically available for treatment of acute SCI, do not inhibit neutrophil activation in this rat model. Taken together, these observations raise a possibility that pharmacological agents that inhibit leukocyte activation used in conjunction with MPS or GM1 may have a synergistic effect in the clinical treatment of traumatic SCI in humans.