The purpose of this study was to explore the optimal therapeutic timing and mechanism of puerarin treatment of spinal cord ischemia–reperfusion injury.The spinal ischemia–reperfusion injury was conducted in male Sprague–Dawley rats, and 50mg/kg of puerarin was injected intraperitoneally at 1, 2, 4 and 6h after the injury. Motor function was measured 48h after reperfusion started. Thioredoxin expression and apoptosis indices were determined.Improvement of motor function at 1, 2, and 4h was demonstrated in the animals with puerarin treatment. Ischemia–reperfusion injury resulted in a decrease in the expression of thioredoxin, while puerarin administration elevated the expression of thioredoxin-1/thioredoxin-2 mRNA. Apoptosis indices were significantly reduced by puerarin administration.We conclude that administration of puerarin within 4h of spinal ischemia–reperfusion injury reduces ischemic reperfusion damage, and that the neuroprotective effect of puerarin involves an increase in the transcription of thioredoxin and a reduction of apoptosis.