The aim of the present study was to evaluate the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 (HIF-1), and to investigate the role of the HIF-1/VEGF signaling pathway following spinal cord injury (SCI). A total of 90 12-week-old Sprague Dawley rats were randomly divided into the following three groups: Sham group (operation without SCI); control group (SCI without ML228 treatment); and treatment group (SCI receiving ML228 treatment). ML228 was administered as it is an activator of HIF-1α. The control and treatment groups were subjected to spinal cord hemisection and motor activity was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring system. Expression of HIF-1α and VEGF in each injured spinal cord section was assessed using immunohistochemistry. Prior to SCI, there were no significant differences in the BBB score among the three groups (P>0.05). However, one day after the operation, the BBB score of the sham group was significantly higher than that of the other two groups (P<0.05) and the BBB scores of the control and treatment groups did not differ significantly (P>0.05). BBB scores 3 and 7 days following surgery were significantly higher in the sham group than the other two groups (P<0.05) and the BBB scores of the treatment group were significantly higher than those of the control group (P<0.05). The expression of HIF-1α and VEGF proteins in all groups were measured 1, 3 and 7 days after the operation, and it was observed that their expression was higher in the treatment group than in the control group (P<0.05). Therefore, the results of the current study suggest that ML228 may effectively activate the HIF-1α/VEGF signaling pathway to promote the expression of HIF-1α and VEGF proteins within the injured segment of the spinal cord, which promotes neural functional recovery following SCI in rats. Therefore, treatment with ML228 may be developed as a novel therapeutic strategy to treat SCI.