Hyperglycemia is known as an exacerbating factor in stroke and many beneficial methods for preventing cerebral ischemia-reperfusion injury have been proved blunting in the diabetic models.Adiponectin (APN) is an adipokine with anti-diabetic and anti-ischemia effects.Electroacupuncture (EA) preconditioning could induce cerebral ischemic tolerance in normal animal models.However, it is unknown whether or not EA can attenuate APN deficiency and cerebral ischemia reperfusion injury in diabetic mice.Male C57BL/6 mice were subjected streptozocin (STZ) for diabetic models.STZ-induced diabetic mice were either untreated or treated with EA (30 min at acupoint "Baihui" with intensity of 1 mA and frequency of 2/15Hz).One hour after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 60 minutes following 24 hours reperfusion.The expression of plasma and cerebral APN levels were measured after 24 hours, as well as the cerebral adiponectin receptors expression.Plasma and cerebral APN levels were decreased in diabetic mice accompanied by decreased cerebral APN receptor 1 (AdipoR1)and APN receptor 2 (AdipoR2).EA pretreatment reduced infarct size, improved neurological outcome and inhibited neuronal apoptosis at 24 hours after reperfusion in the diabetic mice.Further, EA pretreatment unregulated the cerebral expression of APN, as well as AdipoR 1 and AdipoR2.In addition, EA pretreatment decreased cerebral TNF-α and ROS level in diabetic mice compared to the control group.We conclude that pretreatment with EA increases the production of cerebral APN, which elicits protective effects against cerebral ischemia reperfusion injury through AdipoR1 and R2.These results suggest a novel mechanism of EA pretreatment-induced tolerance to diabetic cerebral ischemia.