The aim of this study was to investigate the dose dependent neuroprotective effect of recombinant human erythropoietin (r-Hu-EPO) in acute spinal cord injury induced rats. The rats were allocated into 4 groups of 8 rats each. Spinal cord injury was produced by Yasargil aneurysm clip at a pressure of 0.7 N for a duration of 60 seconds. Group I (Controls) received laminectomy only. Group II (The trauma-only group) had no medication. In group III postoperative intraperitoneal (IP) EPO, total 2000 IU/kg, were applied in two doses. Group IV received postoperative IP EPO in 3 doses, total 9000 IU/kg. In all groups, neuromotor evaluation using Basso's locomotor grading test was conducted at the 6th and 24th hours, and every day from the 1st to 15th days following surgery. After the fifteenth day, all rats were sacrificed and spinal cord samples were obtained for the assessment of caspase-3 activity. The results showed that caspase-3 activity increased to statistically significant higher levels in the spinal cord after injury comparing to the control group. Caspase-3 enzyme activity levels were significantly reduced in animals treated either with low dose or high dose of r-Hu-EPO. In addition, we observed significant difference about rate of functional recovery between group 3 and group 4. Our study showed that high dose EPO administration in the early period after spinal cord trauma increases neurological improvement to a greater degree and in a more rapid manner.