Targeted energy metabolism balance contributes to neural survival during ischemic stroke. Herein, we tested the hypothesis that electro-acupuncture (EA) can enhance cerebral glucose metabolism assessed by F-18-fluorodeoxyglucose/positron emission tomography (F-18-FDG/PET) imaging to prevent propagation of tissue damage and improve neurological outcome in rats subjected to ischemia and reperfusion injury. Rats underwent middle cerebral artery occlusion (MCAO) and received EA treatment at the LI11 and ST36 acupoints or non-acupoint treatment once a day for 7 days. After EA treatment, a significant reduction in the infarct volume was determined by T2-weighted imaging, accompanied by the functional recovery in CatWalk and Rota-rod performance. Moreover, EA promoted higher glucose metabolism in the caudate putamen (CPu), motor cortex (MCTX), somatosensory cortex (SCTX) regions as assessed by animal F-18-FDG/PET imaging, suggesting that three-brain regional neural activity was enhanced by EA. In addition, the AMP-activated protein kinase alpha (AMPK alpha) in the CPu, MCTX and SCTX regions was phosphorylated at threonine 172 (Thr172) after ischemic injury; however, phosphorylation of AMPK was further increased by EA. These results indicate that EA could promote AMPK alpha phosphorylation of the CPu, MCTX and SCTX regions to enhance neural activity and motor functional recovery after ischemic stroke.