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Yiyang Li,1,* Jiali Chen,1,* Xingping Quan,1 Ying Chen,2 Yan Han,1 Jinfen Chen,1 Li Yang,1 Youhua Xu,3 Xu Shen,4 Ruibing Wang,1,5 Yonghua Zhao1,5 1Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macau SAR, People’s Republic of China; 2School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, People’s Republic of China; 4Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghua Zhao, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China, Tel +853-88224877, Fax +853-28841358, Email yonghuazhao@um.edu.moBackground: Ischemic stroke (IS) causes tragic death and disability worldwide. However, effective therapeutic interventions are finite. After IS, blood–brain barrier (BBB) integrity is disrupted, resulting in deteriorating neurological function. As a novel therapeutic, extracellular vesicles (EVs) have shown ideal restorative effects on BBB integrity post-stroke; however, the definite mechanisms remain ambiguous. In the present study, we investigated the curative effects and the mechanisms of EVs derived from bone marrow mesenchymal stem cells and brain endothelial cells (BMSC-EVs and BEC-EVs) on BBB integrity after acute IS.Methods: EVs were isolated from BMSCs and BECs, and we investigated the therapeutic effect in vitro oxygen-glucose deprivation (OGD) insulted BECs model and in vivo rat