Here, with the help of Hk2 cKO mice, we demonstrated that inhibition of microglial HK2 could ameliorate high glucose‐induced poor outcomes of ischemic stroke, which is in consistent with a previous study that inhibition of HK2 with lonidamine could attenuate I/R‐induced brain injury in rat [39], suggesting HK2 as a unifying mediator of metabolic and inflammatory dysfunction across neurological diseases. This evidence concerns the gene HK2 and ischemic stroke.