Stroke is a common disease in the elderly. The high morbidity, mortality and disability of stroke have threatened human health seriously. So far, thrombolytic therapy is the most effective treatment for cerebral ischemic stroke, and tPA is the only thrombolytic drug for the treatment of stroke which has been approved by the US FDA. However, the time window of tPA is only 4. 5 hours and very few people could receive thrombolysis during this period. Moreover, when the therapeutic time window of tPA is more than 4. 5 hours, the incidence of hemorrhagic transformation will significantly increase, then leads to the rapid increase of the mortality of stroke. Clinically, the method of combination therapy is usually used to prolong the therapeutic window of tPA, which is in order to reduce the adverse effects of thrombolysis. HT is one the most serious complications of patients who take the tPA thrombolytic therapy and it limits the clinical application greatly. This article reviews the therapeutic drugs that can be used in combination therapy to expand the therapeutic time window of tPA and at the same time don’t increase the probability of hemorrhagic transformation during animal experiment. We aim to provide a research basis for improving the overall effect of tPA.