This study intends to investigate the effect of 14, 15‐EET on mitochondrial dynamics of neurons induced by middle cerebral artery occlusion (MCAO) and reperfusion in mice, and to elucidate the neuroprotective mechanism of 14, 15‐EET regulating mitochondrial dynamics through AMPK/SIRT1/FoxO1 signaling pathway to alleviate neurological impairment induced by cerebral ischemia–reperfusion, so as to provide a target for the development of drugs for the treatment of cerebral ischemia–reperfusion. This evidence concerns the gene FOXO1 and brain ischemia.