The endothelium (pl.: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall.

Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries.

These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throughout the body.

The endothelium is a thin layer of single flat (squamous) cells that line the interior surface of blood vessels and lymphatic vessels.

Endothelium is of mesodermal origin. Both blood and lymphatic capillaries are composed of a single layer of endothelial cells called a monolayer. In straight sections of a blood vessel, vascular endothelial cells typically align and elongate in the direction of fluid flow.

The foundational model of anatomy, an index of terms used to describe anatomical structures, makes a distinction between endothelial cells and epithelial cells on the basis of which tissues they develop from, and states that the presence of vimentin rather than keratin filaments separates these from epithelial cells. Many considered the endothelium a specialized epithelial tissue. However, much research uncovered not only similarities but also differences between endothelia and epithelia. The comparison is further complicated by the diversity that endothelial cells exhibit.

The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. This forms a barrier between vessels and tissues and control the flow of substances and fluid into and out of a tissue. This controls the passage of materials and the transit of white blood cells into and out of the bloodstream. Excessive or prolonged increases in permeability of the endothelium, as in cases of chronic inflammation, may lead to tissue swelling (edema). Altered barrier function is also implicated in cancer extravasation.

Endothelial cells are involved in many other aspects of vessel function, including: