It has been reported that peroxisome proliferator-activated receptor (PPAR)-gamma agonist, pioglitazone, has several beneficial roles in many pathological states of nervous tissues. Then in the present study, we aimed to examine the neuroprotective actions of pioglitazone (PPAR-gamma agonist) on motor function, histopathological changes and oxidative damage during spinal cord injury (SCI) in rats. Twenty-four male Wistar rats were randomly divided into three groups as follows; sham, control injury and pioglitazone-treated injured groups. SCI was performed according to the Ping-Weight Drop (contusion) model in rat. The animals received pioglitazone (3 mg/kg) intraperitoneally at times of 15 min after injury and then each 12 hours for seven days. At day seven after SCI, the malondialdehyde and glutathione levels were assessed using biochemical techniques. Histopathological alterations in injured spinal cord and motor function recovery were also assessed after six weeks. Induction of SCI in control group significantly increased the malondialdehyde levels (56%, P=0.002) and decreased the content of glutathione (39Â±4 nMol/mL) compared to control group (49Â±6 nMol/mL). Pioglitazone in treated injured rats significantly decreased the malondialdehyde levels (37%, P=0.018) but not glutathione levels (42Â±1 nMol/mL) compared to sham group. In addition, pioglitazone noticeably improved the histopathological changes of injured spinal cord but not motor function. Our findings revealed that pioglitazone decreases histopathological changes and oxidative damage of injured spinal cord. However, it is suggested that pioglitazone must be applied at higher doses for improving motor function during SCI.