The present disclosure provides a method for treating stroke by administering an anticoagulant, e.g., recombinant tissue plasminogen activator (rTPA), and a protein kinase C(PKC) activator, wherein the PKC activator may be administered before, after, or at the same time as the rTPA. The methods disclosed herein may limit the size of infarction and/or reduce mortality, the disruption of the blood-brain barrier, and/or the hemorrhagic damage due to ischemic stroke compared with rTPA administration alone and may also extend the therapeutic time window for administering rTPA after a stroke. Also disclosed are compositions and kits comprising rTPA and a PKC activator for treating stroke.