Background and objectives: Cerebrovascular complications of hypertension are highly dangerous. In recent studies, exosomes have been widely used in several disease research areas, including hypertension research. Mesenchymal stem cells (MSCs) release high levels of exosomes. Therefore, we investigated the role of MSC-derived exosomes in alleviating hypertension-induced changes in the cerebral cortex of a rat model. Methods: A total of 30 rats were assigned to control, hypertensive, and exosome-treated groups which received 100 μg MSC-derived exosomes total protein via tail vein. Tissue samples were examined for gene expression using real-time quantitative polymerase chain reaction (RT-qPCR) and light and electron microscopy. Results and conclusion: Exosome treatment recovered blood vessels, neural cells and blood-brain barrier (BBB) alterations as verified by upregulated endothelial nitric oxide synthase (eNOS) and AMP-activated protein kinase (AMPK) mRNA, downregulated α-smooth muscle actin (α-SMA) mRNA, and enhanced angiogenic factors, miRNA-222 and Tie2 protein. Exosomes exerted anti-apoptotic effects by increasing Bcl-xl expression and decreasing caspase 3 protein levels in immune histochemical sections. The anti-inflammatory potential of exosomes was indicated by reduced IL-1β mRNA and microglia activation factor Iba1 protein levels. Neuronal protection was supported by upregulated miRNA-133b and calbindin D28K (CB) protein levels. Moreover, the astrocyte vascular feet protein aquaporin (AQP4) was downregulated. MSC-derived exosomes may be considered a novel strategy for treating cerebral hypertension complications.