Objective To investigate whether microRNA(miR)-199a-5p regulates blood-brain barrier(BBB) integrity through PI3K/Akt pathway after cerebral ischemia. Methods  A permanent middle cerebral artery occlusion (MCAO) model was established in SPF adult male SD rats. Totally 48 rats were randomly divided into sham group (n=12), model group(n=12), MCAO+miR-199a-5p group(n=12), and MCAO+miR-199a-5p negative control group(n=12). The Ludmila Bellayev 12 point score was used to evaluate the neurobehavioral performance of rats; The integrity of the BBB after ischemia stroke was detected through Evans blue staining; Immunofluorescent staining was used to determine apoptosis after cerebral ischemia; Western blotting technology was used to detect the protein expression of claudin-5, phosphatidylinositol-3 kinase regulatory subunit 2(PIK3R2), p-Akt, Akt, and vascular endothelial growth factor (VEGF)-A; Real-time PCR was used to investigate the expression levels of miR-199a-5p, claudin-5, and VEGF-A in the ischemic penumbra and infarcted area of the brain.  Results The result  showed that miR-199a-5p mimic intervention improved proprioception and motor ability in MCAO rats. MiR-199a-5p mimic reduced the expression of PIK3R2 following ischemia stroke, activated the Akt signaling pathway, and increased the expression of claudin-5 and VEGF-A in the ischemic penumbra. In addition, miR-199a-5p alleviated inflammation after cerebral ischemia. MiR-199a-5p mimic reduced BBB permeability and reduced neuronal apoptosis after cerebral ischemia. Conclusion MiR-199a-5p can reduce the expression of PIK3R2 following ischemic stroke, activate the Akt signaling pathway, reduce the expression of inflammatory cytokines, and alleviate the damage to the blood-brain barrier.