Aim To observe the changes of the ultrastructure and expression of Klotho,intercellular adhesion molecular-1(ICAM-1)and vascular cellular adhesion molecular-1(VCAM-1)genes in the brain tissue of the spontaneously hypertensive rat model treated by medicines. Methods 10 male spontaneously hypertensive rats of 22 weeks age were selected and randomly divided to hypertension and Fosinopril interventive groups,while 5 Wistar-kyoto rats were setted as normal contrast group. The brain ultrastructure of all groups were observed by electron microscope. The expression status of micro-inflammatory factor(ICAM-1 and VCAM-1)and Klotho gene were detected with RT-PCR,immunohistochemistry and western blotting. Results Hypertension might affect the structures of brain neuron,such as nucleus aggregation,nucleus condensation,nucleus fragmentation and apoptotic body formation. But fosinopril treatments could reduce the damage of brain neuron. By RT-PCR Fosinopril treatments could up-regulate the mRNA expression of Klotho gene(P><0.05) and down-regulate the mRNA expression of ICAM-1 and VCAM-1gene in the brain tissue of the SHR group(P><0.01). At the same time,the results of immunohistochemistry and western-blot verified that fosinopril increased the protein expression of Klotho and depressed the protein expression of ICAM-1 and VCAM-1. These results suggested that fosinopril could protect the neuron function by regulating the expression of Klotho gene and ICAM-1 and VCAM-1. Conclusion Fosinopril could resume the ultrastructure in the brain tissue of the spontaneously hypertensive rat.