Background Erythropoietin (EPO) functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective effect of erythropoietin on experimental rats enduring spinal cord injury (SCI) by assessing thrombospondin-1 (TSP-1) level and transforming growth factor-β (TGF-β) in the development of a rat model of SCI. Methods Sixty Sprague-Dawley rats were randomly assigned to three groups: sham operation control group, SCI group and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were sacrificed at 24 hours and 7 days subsequently. The Basso, Beattie, and Bresnahan (BBB) scores were examined for locomotor function. Pathological changes were observed after HE staining. The expressions of thrombospondin-2 (TSP-1) and TGF-β were determined by immunohistochemical staining and Western blotting. Results Slighter locomotor dysfunction was discovered and it was recovered abruptly as higher BBB scores were found in the EPO treatment group than in the SCI group (P