The article reviews the molecular mechanisms regulating vascular endothelial permeability, which is crucial for maintaining homeostasis and preventing diseases such as edema, cancer, and atherosclerosis. Endothelial cells form a continuous monolayer lining the inner wall of blood vessels, acting as a selective barrier to control the exchange of fluids, solutes, and cells between blood and tissues. The barrier function is regulated by two main pathways: the transcellular and paracellular pathways. The transcellular pathway involves the transport of substances across the endothelial cytoplasm, while the paracellular pathway involves the opening and closing of endothelial cell adhesions through tight and adherens junctions. Key molecules involved in these pathways include VE-cadherin, which plays a critical role in adherens junctions, and small GTPases like RhoA and Rac1, which regulate actin dynamics and cell adhesion. Additionally, factors such as vascular endothelial growth factor (VEGF) and angiopoietins can modulate endothelial permeability by affecting the phosphorylation of VE-cadherin and the activity of other signaling molecules. Inflammatory mediators and fluid shear stress also contribute to the regulation of endothelial permeability. Understanding these mechanisms is essential for developing therapeutic strategies to prevent and treat diseases associated with endothelial dysfunction.The article reviews the molecular mechanisms regulating vascular endothelial permeability, which is crucial for maintaining homeostasis and preventing diseases such as edema, cancer, and atherosclerosis. Endothelial cells form a continuous monolayer lining the inner wall of blood vessels, acting as a selective barrier to control the exchange of fluids, solutes, and cells between blood and tissues. The barrier function is regulated by two main pathways: the transcellular and paracellular pathways. The transcellular pathway involves the transport of substances across the endothelial cytoplasm, while the paracellular pathway involves the opening and closing of endothelial cell adhesions through tight and adherens junctions. Key molecules involved in these pathways include VE-cadherin, which plays a critical role in adherens junctions, and small GTPases like RhoA and Rac1, which regulate actin dynamics and cell adhesion. Additionally, factors such as vascular endothelial growth factor (VEGF) and angiopoietins can modulate endothelial permeability by affecting the phosphorylation of VE-cadherin and the activity of other signaling molecules. Inflammatory mediators and fluid shear stress also contribute to the regulation of endothelial permeability. Understanding these mechanisms is essential for developing therapeutic strategies to prevent and treat diseases associated with endothelial dysfunction.