Background and objective: Endothelial cell inflammation caused by mechanical injury of endovascular treatment remains the major obstacle to reendothelialization, which leads to arterial restenosis. We investigated the reendothelialization effect of exosomes from adipose-derived mesenchymal stem cells (ADSC) overexpressing Stanniocalcin-1 (STC-1).Methods: Primary ADSCs were extracted from the adipose tissue of the inguinal area of C57/BL mice. ADSCs were transfected with lentivirus vectors containing STC-1. Exosomes were purified from culture medium using the Exo-Quick kit and characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot. PHK-26 as molecular probe was used to track the exosomes engulfed by mice arterial endothelial cells (MAEC). The role of STC-1-ADSC-Exosome (S-ADSC-Exo) in MAECs was verified through scratch test and tube forming experiment. Carotid endarterium mechanical injury was induced by insertion with a guidewire into the common carotid artery lumen. Exosomes were administered by tail vein injection. Content of Reactive oxygen species (ROS) was measured using commercial kits. Carotid arteries were harvested for histological examination, immunofluorescence staining, and Evan’s blue staining.Results: Transfection of STC-1 significantly enhanced STC-1 levels in ADSCs, their exosomes, and MAECs. Compared with the control group and the ADSC-Exo group, STC-1 enriched exosomes markedly enhanced STC-1 level, inhibited the expression of NLRP3, Caspase-1, and IL-1β in MAECs, exhibited good lateral migration capacity, and promoted angiogenesis. Exosome-pretreating groups exhibited lower levels of ROS than those of controls. In vivo administration of S-ADSC-Exo had reendothelialization effect on post-injury carotid endarterium as evidenced by thinner arterial wall, low-expressed NLRP3, and more living endothelial cells.Conclusions: The reendothelialization effect of exosomes from ADSCs on post-injury carotid endarterium can be enhanced by genetic modification to contain elevated STC-1.