This study investigated the mechanisms responsible for the neuroprotective effect of sildenafil citrate (SFC) on ischemia-reperfusion spinal cord (SC) injuries. Balloon occlusion of the thoracic aorta was used to induce SC ischemia. The animals (n=30) were separated into three groups: sham, SC injury with saline, and SC injury with 5mg/kg i.p. SFC treatment (SFC). The Basso, Beattie, and Bresnahan (BBB) score was determined to assess neurological function at different time intervals after reperfusion. After 48h, histopathology of the SC was assessed by triphenyltetrazolium chloride (TTC) and Nissl staining. Myeloperoxidase (MPO) activity was estimated using an MPO assay kit. Western blot and ELISA assays were performed to estimate interleukin 1 & 10 (IL-1 & IL-10), tumour necrosis factor α (TNF-α), and nuclear factor (NF-kB) levels in SC tissue homogenates. The study results suggest that treatment with SFC significantly increased neurological function compared with the SC group. In addition, SFC treatment reduced MPO activity compared with the SC group, which subsequently inhibited the infiltration of neutrophils into the SC. There was a significant (p<0.01) decrease in the expression of IL-1 and TNF-α, and an increase in the expression of IL-10 in SFC tissue homogenates compared with SC tissues. Moreover, SFC treatment inhibited the activation of NF-kB in the SC after injury. This study shows that SFC exerts a neuroprotective effect on the SC after ischemia/reperfusion injury by attenuating inflammatory mediators.