Objective To explore the effect of sufentanil postconditioning on the focal cerebral ischemia reperfusion injury in diabetic rats. Methods An intraperitoneal injection of 50 mg/kg streptozotocin was used to induce diabetes in rats. Meanwhile, the diabetes mellitus model was confirmed by the blood glucose level over 16.7 mmol/L. The diabetes mellitus male SD rats, weighting 250-300 g, were randomly divided into 3 groups: sufentanil postconditioning diabetic group (SP-DM), ischemia reperfusion diabetic group (IR-DM), sham operation diabetic group(sham-DM), with 12 in each group. The non-diabetic rats were randomly divided into 3 groups: sufentanil postconditioning non-diabetic group(SP-NDM), ischemia reperfusion non-diabetic group(IR-NDM), sham operation non-diabetic group(sham-NDM), with 12 in each group. All rats in the IR-NDM/DM group and SP-NDM/DM group were exposed to the right middle cerebral artery occlusion for 90 minutes followed by 24 hours reperfusion. The sufentanil 1 μg/kg were injected into the rats in SP-NDM/DM group via tail vein at 5 minutes before reperfusion. Normal saline was injected into the rats in sham-NDM/DM group and IR-NDM/DM group at 5 minutes before reperfusion. At 24 hours after reperfusion, the neurological deficit scores(NDS) were assessed, then all the rats were sacrificed.Infarct volume, which was determined by 2, 3, 5-triph-enyltetrazolium (TTC)staining, and water content of right hemisphere for brain edema were also measured. Results All rats showed neurological deficit, brain infarction and brain edema after focal cerebral ischemia reperfusion. (1)At 24 hours after reperfusion, the neurological deficit score in IR-DM group(3.4±0.4) was significantly higher than that in the IR-NDM group(2.8±0.5)(t=2.313, P 0.05). (2) At 24 hours after reperfusion, the infarct volume in IR-DM group((58.3±2.1)%) was significantly higher than that in the IR-NDM group((32.1±2.6)%)(t=2.912, P 0.05). (3)At 24 hours after reperfusion, the water content of the right hemisphere in IR-DM group((89.3±3.5)%) was significantly higher than that in the IR-NDM group((82.6±3.9)%)(t=2.218, P 0.05). Conclusion Sufentanil postconditioning loses neuroprotection against focal cerebral ischemia reperfusion injury in diabetic rats. Key words: Focal cerebral ischemia reperfusion injury; Sufentanil; Postconditioning; Diabetes; Rat