The vast heterogeneity of endothelial cells (EC) in various organs necessitates isolation of EC from the relevant organs when defining mechanisms of site-specific pathologies. We report a novel finding that describes the presence of two heterogeneous populations of human nasal microvascular endothelial cells (HNMEC) isolated from the inferior turbinate. Light and electron microscopy, flow cytometric and immunocytochemistry analysis demonstrated that one EC population exhibited the classic vascular endothelial markers with cobblestone-like morphology, while the other was sinusoidal with fusiform morphology. The sinusoidal EC lacked surface expression of the two endothelial markers CD31 and E-selectin, were discontinuous, showed fenestrae and pinocytic vesicles and did not form tight junctions. Gene expression analysis using microarray revealed significant but limited heterogeneity between the two cell types. Immunohistochemical staining of normal nasal biopsies confirmed the presence of two distinct populations of EC. We found that CD31 was exclusively expressed on vascular EC, while the molecule L-SIGN was mainly expressed on sinusoidal EC. In vitro both cell types formed capillary-like tubules in matrigel. The two heterogeneous EC populations provide a unique in vitro system to study the biology of nasal vascular and sinusoidal EC in normal conditions as well as inflammatory processes in various nasal disorders.