Vascular endothelial dysfunction plays an important role in the pathogenesis of atherosclerosis. As a protective barrier of vascular endothelium, glycocalyx plays a series of protection role, including regulation of vascular permeability, mediating the release of nitric oxide (NO) induced by shear stress, inhibition of the adhesion between leukocytes, platelets and endothelial cells, anticoagulation. This article reviews the important meaning of glycocalyx’s integrity and its endothelial protection, and its relationship with atherosclerosis.