Daidzein (DZ) has a broad spectrum of biological activities, including antioxidant, anti‑inflammatory and anticancer as well as cardio‑ and hepatoprotective properties. The present study was designed to elucidate the in‑depth mechanism underlying the neuroprotective efficacy of DZ against spinal cord ischemic/reperfusion injury (SCII) in a rat model by comparison with the standard neuroprotective agent methylprednisolone (MP). A total of 48 rats were divided into four groups of twelve rats in each (n=12). In sham‑operated group (Control) group, rats received only saline (Fogarty catheter was inserted without balloon inflation), whereas rats in the SCII induction group (SCII) were subjected to SCII insult by insertion of a Fogarty balloon catheter, which was inflated in the descending thoracic aorta to cause an occlusion. A proportion of rats was treated with DZ (20 mg/kg; DZ+SCII group) or MP (50 mg/kg; MP+SCII group) for seven days prior to and after SCII. The locomotor function (neurological activity) and antioxidant levels (superoxide dismutase and catalase) levels were significantly improved upon treatment with DZ and MP in comparison with those in the SCII group. A concomitant decline in edema, inflammatory markers (myeloperoxidase, tumor necrosis factor‑α and nuclear factor κB p65), the apoptotic marker caspase‑3 and the number of cells with terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling was also observed in the DZ and MP groups. The protein levels of phosphoinositide‑3 kinase (PI3K), the phosphorylated Akt/Akt ratio and B‑cell lymphoma 2 (Bcl‑2) were substantially downregulated, while Bcl‑2‑associated X protein levels were upregulated SCII insult group, which was inhibited by treatment with DZ. To conclude, pre‑treatment with DZ significantly improved the neurological function by upregulating PI3K/Akt signaling and thereby considerably attenuating the inflammatory response and apoptosis, thus maintaining the neuronal count in an SCII‑induced rat model.