Aim: To observe the changes of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in rats with focal cerebral ischemia-reperfusion injury, and study the role of fibrinolysis. Methods: The experiment was performed in the Department of Neurology, First Clinical Hospital of Jilin University from 2001 to 2003. Totally 48 male Wistar rats were divided randomly into control group (n=6), sham operation group (n=6) and experimental group (n=36) including 90 minutes, 0, 6, 12, 24, 48 and 72 hours of ischemia groups (n=6). Rats in control group received no treatment but in experimental group were made into models of focal ischemia-reperfusion by using the filament occlusion method; the filament did not reached to the middle cerebral artery of rats in sham operation group. The time of ischemia lasted for 90 minutes. Rats in experimental group were decollated to extract brain tissue at different time points of ischemia-reperfusion. The expression of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in rats were detected by using immunohistochemistry and in situ hybridization methods. Apoptosis neurons were detected by using TUNEL. Results: All 48 rats were involved in the result analysis. 1 The slight expression of tissue-type plasminogen activator protein and mRNA, and plasminogen activator inhibitor-1 protein and mRNA in rats was found in cerebral cortex and putamen neurons of tail. 2 The expressions of tissue-type plasminogen activator protein and mRNA, and plasminogen activator inhibitor-1 protein and mRNA were different at different time points: At the very beginning of reperfusion, the positive expression of tissue-type plasminogen activator protein and mRNA was detected mainly in normal neurons. The expression increased gradually, reached to the peak after 48 hours and maintained until the 72nd hour after reperfusion. The expression of plasminogen activator inhibitor-1 protein and mRNA increased later as compared with that of tissue-type plasminogen activator protein and mRNA, and reached to the peak at 72 hours after reperfusion. Positive neurons of tissue-type plasminogen activator protein and plasminogen activator inhibitor-1 protein were detected at the regions of the ischemic core in cortex and basal ganglia and showed slighter at the border regions. 3 Few apoptotic cells were detected in ischemic cerebral cortex and putamen of tail at the beginning of reperfusion and reached to the peak at 48-72 hours. Conclusion: Tissue-type plasminogen activator protein plays an important role in ischemic injury. Its trigger of apoptosis is included in the mechanisms of ischemic injury. The delayed expression of plasminogen activator inhibitor-1 protein may be induced by the increased tissue-type plasminogen activator protein.