Objective To study the effects of cromakalim on cerebral infarction volume, mGluR1α, GLT-1 after cerebral ischemic reperfusion. Methods Male Wistar rats were randomized into three groups ( n = 20 sham-operated group, MCAO group , MCAO+ATP sensitive potassium channel openers (cromakalim) group. Intraluminal thread methods were applied to establish the middle cerebral artery occlusion reperfusion models in the mice, At the 24h after the reperfusion, the nervous behavioral function was evaluated with Bederson’s test, the cerebral infarction volume was observed with tetrazolium chloride staining. mGluR1α and GLT-1 were detected by immunohistochemistry method. Results At the 24 h after cerebral ischemic reperfusion injury, neurological behavioral malfunction appeared in all the mice, the score of neurological behavioral function in group C （2.23±0.11）was improved compared with that in group B（2.61±0.19）(P <0.05); Focus of cerebral infarction was found in the ischemic hemisphere of the brain, the cerebral infarction volume in group C （138.3±29.9）was significantly reduced compared with that in group B（182.5±34.5）(P <0.05)；the absorbance of mGluR1α in group B （0.293±0.009）was increased compared with that in group A（0.183±0.008），the absorbance of GLT-1 in group B（0.147±0.009） was increased compared with group A（0.255±0.009）(P <0.05), the absorbance of mGluR1α in group C （0.227±0.009）was decreased compared with group B（0.293±0.009）(P <0.05)； the absorbance of GLT-1 in group C（0.212±0.008） was increased compared with group B（0.147±0.009）(P <0.05).Conclusion Reducing ischemia reperfusion injury through the preventive use of Cromakalim may be related to decreasing the expression of mGluR1α, increasing the expression of GLT-1, inhibiting the accumulation of glutamic acid, and reducing the cerebral infarction volume.