Objective To investigate the clinical efficacy of intravenous recombinant tissue plasminogen activator（ rt-PA） thrombolysis in patients with acute major cerebral artery occlusion and discuss its potential problems. Methods A retrospective study was performed to analyze 165 consecutive patients who received intravenous rt-PA thromblysis in PLA army General Hospital from January 2014 to August 2016. The occlusion site on MRA imaging， National Institute of Health Stroke Scale（ NIHSS） score at admission and 24 hours after thrombolysis， recanalization of occlusion artery after one month， and the modified Rankin scale（ mRS） score after three months were all documented and further compared and analyzed. Results In the 165 patients included， 89 cases were due to major arterial occlusions and the other 76 cases were without major artery occlusion. The NIHSS score of non-aortic occlusion group was significantly improved after intravenous thrombolysis compared with that of aortic occlusion group， and the mRS score was better at 3 months（ P ＜ 0.05）. Of the 89 cases of major artery occlusion， there were 43 cases occluded in internal carotid artery（ ICA）， 25 cases in middle cerebral artery（ MCA） and 21 cases in vertebrobasilar artery（ VBA）. The ICA and MCA groups enjoyed a better 3-month mRS scores compared to VBA group（ P＜ 0.05）. According to pathogenesis of occlusion， 89 cases could be divided into thrombosis subgroup with 69 cases and embolism subgroup with 20 cases. The embolism subgroup enjoyed better 3-month mRS scores compared to thrombosis subgroup （P ＜ 0.05）. Totally 70 cases received recanalization follow-up review， and the recanalization rates was 21.4%. The occlusion sited or occlusion pathogenesis did not show significant difference in recanalization（ P=0.133， 0.779）. Conclusions For acute stroke caused by major artery occlusion， the efficacy of intravenous rt-PA thrombolysis is not obvious in the recanalization rate and 3-month outcome improvements.