Objective To investigate salvinorin A (SA) as a ischemic stroke protector after the incidence of ischemic stroke by promoting upregulation of LcnRNA MALAT1 in cerebrovascular endothelial cells, inhibiting phosphorylation of mitochondrial division protein (Drp1) and attenuating mitochondrial damage. Methods 60 male SD rats, weighed 200~250g, were randomly divided into 4 groups （15rats each）. In the sham surgery group (S group), carotid artery of rats were isolated from one side without any intervention; in MCAO group，the internal carotid artery on one side was blocked with a wire embolus for 60 min and the wire embolus was withdrawn for reperfusion; in the salvinorin A group (SA group), SA (2ug/kg) was given via the tail vein immediately after internal carotid reperfusion; in the SA antagonist group (NB group), norBIN (2mg/kg) was given 30 min before SA injection and pretreated with SA; 24 hours after MCAO, cerebral infarct area (TTC), blood-brain barrier permeability (Evansblue) were measured, and neural assessment was performed 1, 2 and 5 days after MCAO. In vitro experiments were performed using a human cerebrovascular endothelial cell (HBMEC) hypoglycemic hypoxia (OGD) model, in which 6h of hypoxia was followed by 24 h of reoxygenation, SA (2uM) and norBIN (1uM) were added immediately after reoxygenation, and LcnRNA MALAT1 expression was interfered with by siRNA technology. HBMEC was subjected to OGD and CCK8 determined HBMEC viability, pDrp-1/Drp-1, ROS levels, and the morphology of morphology was observed under electron microscope. Results The infarct size of the SA group was significantly reduced, evansblue exudation was significantly reduced, and the motor nerve function of the MCAO rats was significantly improved. After norBIN treatment, the role of SA was antagonized, the infarct size increased, vascular permeability increased, and nerve function decreased. The cell viability of HBMEC after SA treatment was significantly increased. Under electron microscopy mitochondrial morphology tends to be normal , the expression levels of pDrp-1/ Dpr-1 were significantly down-regulated, and the ROS content decreased. After NB group and MALAT1 interference, cell viability decreased, pDrp-1 / Dpr-1 expression increased, ROS increased, and the mitochondrial morphology was destroyed Conclusion The κ opioid receptor agonist SA attenuates mitochondrial damage in cerebrovascular endothelial cells after ischemic stroke by stimulating the secretion of MALAT1, attenuates oxidative stress in HBMEC, and improves brain function.SA plays a protective effect in ischemic stroke.