To explore the impact of electro-acupuncture on the expression of CREB in the ischemia-reperfusion rats. Methods： Sixty healthy adult SD rats which were domesticated for 3 days were randomly divided into the shame group, the model group and the electro-acupuncture group. There were 20 rats in each group. The rats of the model group and the electro-acupuncture group were given the line bolt method (MCAO) to complete the brain ischemia model, and were reperfused 2 hours after ischemia. The electro-acupuncture group adopted the intervention of electro-acupuncture. Three days after the reperfusion, all the rats were beheaded and taken brains. The cerebral infarction volume was observed through TTC staining and image analysis, and the protein expression of CREB were detected by protein imprinting method (Western blotting) and gene expression of CREB were tested by Real-Time PCR. Results： TTC and the image analysis showed that the cerebral infarction volume of electro-acupuncture group was significantly smaller than that of the model group (P<0.01); the CREB protein level in the electro-acupuncture group was obviously higher than that of the model group (P<0.01); the CREB gene level in the electro-acupuncture group was much higher than that of the model group (P<0.01). Conclusion： Electro-acupuncture can realize the improvement of the cerebral ischemia reperfusion injury by up-regulating CREB.