The development of microcirculation imaging devices has significantly advanced our comprehension of the capillary environment's dynamics. Early research suggested that erythrocytes did not contact the vessel's inner surface due to the Fåhraeus effect, implying the presence of a covering on the endothelial cell surface. Subsequent electron microscopy studies revealed this layer to be a complex part of the vessel wall, now known as the endothelial glycocalyx (EG). The EG is a network of proteoglycans and glycoproteins bound to the endothelial membrane, incorporating soluble molecules from the endothelium and plasma. Over time, studies have elucidated the structure, function, and therapeutic targets of the glycocalyx, underscoring its pivotal role in vascular biology. The presence of cellular extensions of lung tissue cells in both vascular and nonvascular areas demonstrates the pivotal role of the glycocalyx in pulmonary vascular leak, surfactant dysfunction, impaired lung compliance and gas exchange abnormalities, which are hallmarks of acute respiratory distress syndrome (ARDS). It is of the utmost importance to elucidate the mechanisms underlying alveolocapillary glycocalyx degradation to develop efficacious treatments for ARDS, which has a mortality rate of 35 %. An understanding of the glycocalyx's role in vascular integrity provides a foundation for exploring new therapeutic avenues to mitigate lung injury and improve clinical outcomes in ARDS patients.