Overall, our findings support the hypothesis that circPTP4A2 triggers microglial M1 polarization by activating STAT3 phosphorylation and that subsequent knocking down circPTP4A2 inhibits STAT3 phosphorylation and shifts microglial polarization from M1 to M2 phenotype, resulting in neuroprotective effects after ischemic stroke. Here, STAT3 is linked to ischemic stroke.