Hyaluronan (HA) is the only nonsulphated glycosaminoglycan of extracellular matrix. In mammals HA is synthesised by three homologues HA synthases: HAS1, HAS2, and HAS3. The HA is daily catabolized by the hyaluronidase enzymes to either oligosaccharides or larger polymer. Despite its simple structure, HA is involved in a great number of biological functions, such as cell proliferation and migration, morphogenesis, wound healing, inflammation, angiogenesis, and tumor growth. Moreover, an important biological role is related to HA oligosaccharides that stimulate cytokine secretion and endothelial cell proliferation. Nevertheless no data about HA presence in endothelium are reported in literature. Several studies underline HA involvement in endothelial cell proliferation, migration, new vessels formation, and leucocytes recruitment. We review the role of HA in endothelial cell in normal condition and during vascular injury.