In the present study, we found that ischemia-induced HIF-1α is involved in the transcription of Irak3. Then we used Irak3-null mice for the first time to investigate the role of IRAK-M in cerebral ischemia, and found IRAK-M deficiency increased infarct volume, brain edema, incidence of hemorrhage transformation, BBB permeability, and levels of inflammatory responses. The gene discussed is IRAK3; the disease is brain ischemia.