To better bridge this gap and understand the mechanism of stem cell-derived EVs treatment after ischemic stroke, in this study, we investigated the therapeutic effects of BMSC-derived small EVs (sEVs) on BBB injury in cerebral ischemia/reperfusion model, and firstly illustrated the mechanism was related to Cav-1 mediated autophagic degradation of tight junction protein ZO-1 and Occludin. This evidence concerns the gene CAV1 and ischemic stroke.