AbstractThe endothelial glycocalyx covers the lumen of blood vessels throughout the body and plays an important role in endothelial homeostasis. Advances in electron microscopy techniques have provided clues to better understand the structure and composition of identical vascular endothelial glycocalyx. The morphology and thickness of the endothelial glycocalyx differ from organ to organ. The content of the endothelial glycocalyx covering the vascular lumen differs even in the brain, heart, and lungs, which have the same continuous capillaries. Various types of inflammation are known to attenuate the endothelial glycocalyx; however, we found that the morphology of the glycocalyx damaged by acute inflammation differed from that damaged by chronic inflammation. Acute inflammation breaks the endothelial glycocalyx unevenly, whereas chronic inflammation leads to the overall shortening of the endothelial glycocalyx. The same drug has different effects on the endothelial glycocalyx, depending on the location of the target blood vessels. This difference in response may reflect not only the size and shape of the endothelial glycocalyx but also the different constituents. In the cardiac tissue, the expression of glypican‐1, a core protein of the endothelial glycocalyx, was enhanced. By contrast, in the pulmonary tissue, the expression of heparan sulfate 6‐O‐sulfotransferase 1 and endothelial cell‐specific molecule‐1 significantly increased in the treatment group compared with that in the no‐treatment group. In this review, we present the latest findings on the evolution of the vascular endothelial glycocalyx and consider the microstructural differences.