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Following ischemic stroke, bloodbrain barrier (BBB) is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia.BBB breakdown promotes inflammation infiltration into the brain, which exacerbates cerebral ischemic injury as a result.Here, we report that 10O(N,Ndimethylaminoethyl)ginkgolide B methanesulfonate (XQ1 H), a novel analog of ginkgolide B, alleviates BBB breakdown in hyperlipidemic rats and protects endothelial cells against inflammatory response.Middle cerebral artery occlusion (MCAO) modeled ischemic stroke in rats.Before surgery, these rats were fed a cholesterolrich diet to induce an experimental hyperlipidemic condition.Additionally, lipopolysaccharide (LPS) incubation with rat brain microvessel endothelial cells(rBMECs) was applied to mimic hyperlipidemiainduced inflammatory injury of BBB.The results indicated more severe infarct size, increased BBB permeability, excessive secretion of proinflammatory cytokines, and exaggerated inflammation infiltration of the brain in hyperlipidemic rats following MCAO when compared to rats fed with normal diet.XQ1H protected BBB integrity, lessoned brain edema and inflammation penetration, downregulated MMP9 and VCMA1 expressions, and extenuated ischemic infarction.XQ1H alleviated LPSinduced inflammatory response in rBMECs, characterized by promoting cell viability, inhibiting TNFα, IL1β, and IL6 releasing, and downregulating NFκB inflammatory signal and downstream proteins, such as VCAM1 and iNOS.In conclusion,the present study shows that XQ1H stabilizes BBB function following ischemic stroke in hyperlipidemic rats, and the possible mechanisms may be related to inflammation inhibition.