NLRP3/ASC/Caspase-1 mediated pyroptosis is one of the important causes of cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture (EA) is widely used in clinical treatment of ischemic stroke. However, mechanism of EA on ischemic stroke remains unclear. Therefore, on basis of a previous work, this study used middle cerebral artery occlusion (MCAO) 2 h and then reperfusion 7 days in rats to simulate brain I/R process. EA with Bahui (GV20) and Zusanli (ST36) and VX-765 (a specific inhibitor of Caspase-1) was performed. In this study, we found that EA improved cerebral infarct size and neuronal damage, including ultrastructural injury, and ameliorated nitro/oxidative stress in cerebral I/R. Additionally, EA treatment significantly decreased ASC, Caspase-1, GSDMD, and IL-1β expression and VX-765 treatment significantly decreased NLRP3, Caspase-1, and IL-1β expression. This proved that EA can regulate NLRP3/ASC/Caspase-1 mediated pyroptosis, improve neuronal injury during cerebral I/R, and provide basic experimental data for clinical treatment.