The main findings of this study are (1) in the ipsilateral hemisphere, ASK1 silencing resulted in a reduction of ischemic-induced activation of microglia/infiltrated macrophages and increased M2 phenotype in the late phase of cerebral ischemia and (2) ASK1 inhibition polarized BV2 microglia and RAW 264.7 macrophage cell lines toward M2 phenotype after hypoxia/reperfusion injury. This evidence concerns the gene MAP3K5 and brain ischemia.