Therefore, this study employed Microglia‐specific conditional MK5 knockout (MK5 cKO) mice to knockout microglial MK5 in the brain, followed by middle cerebral artery occlusion (MCAO), while BV2 cells were transfected with small interfering RNA (siRNA) to knock down MK5 levels, and subsequently exposed to oxygen–glucose deprivation/reperfusion (OGD/R) to investigate the role of microglial MK5 in microglial activation and ischemic stroke progression. The gene discussed is MAPKAPK5; the disease is ischemic stroke.