While ex-vivo studies have shown that small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) can be internalized by neurons leading to enhancement of neurite remodeling, whether such communication are present in ischemic brain is not known. Using CEC-sEV reporter mice, we investigated whether endogenous CEC-sEV mediate communication between CECs and neural cells after stroke. A CEC-specific/sEV reporter mouse line was generated by crossing Slco1c1- CreERT2 mice with CD63-GFP loxP/loxP mice. The adult reporter mice were subjected to middle cerebral artery occlusion or sham operation after tamoxifen injection (n=4/group). 3D confocal microscopic analysis revealed that GFP signals in sham operated reporter mice were primarily localized within cerebral vessels, while extravascular GFP signals were also detected throughout the entire brain, suggesting that endogenous sEVs are specific to CECs and CEC-sEVs are released into brain parenchyma. Compared to the sham mice, ischemia induced robust angiogenesis in the peri-infarct areas assessed by increasing vascular density at day 7 and 42 post stroke, where the GFP signals within endothelium increased by 56% and 28%, respectively. The GFP signals within parenchyma (outside of vessels) of the peri-infarct areas were augmented by 21% and 24% at day 7 and 42 post stroke, respectively, suggesting that stroke increases CEC-sEVs secretion at peri-infarct angiogenic sites. Immunofluorescent staining showed that the increased parenchymal GFP signals in peri-infarct areas were localized within GFAP + astrocytes by 36% and 21% of total parenchymal GFP signals at day 7 and 42 post stroke, respectively. Moreover, the GFP signals within the peri-infarct MAP2 + neurons were significantly augmented by 22% at day 42 but not at day 7 after stroke compared to the sham group. Stroke did not alter GFP signals within IBA1 + microglia in the reporter mice. In conclusion, our in vivo data for the first time demonstrate that stroke increases the release of CEC-sEVs at peri-infarct angiogenic sites, where they actively communicate with astrocytes and neurons during stroke recovery. These data suggest that endogenous CEC-sEVs may regulate neurovascular function contributing to stroke recovery.