Abstract: Objective：To investigate the therapeutic effect of exosomes drived from human umbilical vein endothelial cells on ischemic stroke. Methods：Exosomes derived from human umbilical vein endothelial cells (HUVECs) were isolated and identified. Exosomes of 30μg (dissolved in 100 μL of PBS) or an equal volume of PBS were injected intravenousl into the transient ischemic model of the middle cerebral artery. mNSS scores were performed on mice after ischemic stroke on day1,3, 7, 14, and 28, respectively. MRI imaging were used to observe the infract size.All mice were sacrificed on day 28 after surgery,CD31/ BrdU、DCX/BrdU and NeuN/BrdU immunofluorescence double staining were applied to detected angiogenesis and neurogenesis in the ischemic boundary zone. In order to evaluate synaptic plasticity, the expression of synaptophysin and PSD-95 in the ischemic boundary zone were detected with Western blot. Result：The infarct size of HUVECs-exo group was significantly reduced compared to PBS group（P<0.05）. Compared to PBS group, newborn blood vessels, neural precursor cells, and mature neurons in the ischemic boundary were significantly higher in HUVECs-exo group, respectively（P<0.05）. The expression of synaptophysin and PSD-95 of HUVECs-exo group in the ischemic boundary were significantly higher when compared to PBS group（P<0.05）. There was no significant difference in mNSS scores of mice between HUVECs-group and PBS group on day 1、3、7 after surgery,but that were significantly lower in HUVECs-exo group on day 14、21、28 compared to PBS group. Conclusion：HUVECs-exo can reduce infract size,improve angiogenesis,neurogenesis and synaptic plasticity in the ischemic boundary zone after ischemic stroke and finally improve the neurological outcome.