Objective: To investigate the effects and mechanisms of Oncostatin M (OSM) on spinal cord ischemia and reperfusion injury in rat model. Methods: Thirty healthy male Sprague-Dawley (SD) rats were randomly divided into two groups in the first part of the experiment: spinal cord ischemia and reperfusion group (I/R group): 24 rats underwent abdominal aorta occlusion for 30 min, then 6 in the 3 h post reperfusion, 6 in the 6 h post reperfusion, 6 in the 24 h post reperfusion and 6 in the 72 h post reperfusion, and 6 rats were in the sham-operated control group (Control group). The neurological function was evaluated by Modified Tarlov score. Myeloperoxidase (MPO) activation of the spinal tissue in each group was detected. The expression of OSM was measured by real-time PCR after reperfusion. Twenty-four rats were divided into 2 groups in the second experiment, 12 rats were injected with OSM (I/R+OSM group) and 12 rats were injected with PBS (I/R+PBS group), The neurological function and MPO activation were evaluated after 24 h; the activation of STAT3 protein was detected by Western Blot. Results: After spinal cord ischemia and reperfusion, the neurological function injury was serious and the expression of MPO increased gradually in the spinal tissue; OSM expression increased significantly 6 h after reperfusion; 24 h after local injection of OSM to the rats with spinal cord ischemia and reperfusion injury, the expression of p-STAT3 protein increased, and the neurological function of rats significantly improved, while MPO activation decreased. Conclusions: The OSM/STAT3 signal pathway plays a protective role in the spinal cord ischemia and reperfusion injury.