In the present study, we observed elevations of mRNA levels of proinflammatory cytokines (i.e., TNF-α, IL-1β, and IL-6) in the ipsilateral hemisphere and the stronger activation of astrocytes and microglia/macrophages in the ischemic brain in tPA-infused tMCAO mice, which were significantly inhibited by combined treatment with tPA and CD21, suggesting that CD21 inhibited the tPA-induced neuroinflammatory response after ischemic stroke. Here, IL1B is linked to ischemic stroke.