BST2 is a type II transmembrane protein that had been initially identified as a surface molecule expressed on terminally differentiated B cells. Here, we characterize the expression of BST2 in human endothelial cells, HUVECs. IFN-γ, among various inflammatory stimuli, dramatically upregulates BST2 expression in HUVECs. We also address a novel putative role of BST2 in IFN-γ-stimulated HUVECs as an intercellular adhesion-related molecule. We show that purified extracellular domain of BST2 protein specifically and significantly decreased the adhesion of human monocytes to HUVECs, which suggests that IFN-γ-induced BST2 expression may be involved in monocyte migration from blood through the endothelium to the inflammation site. Furthermore, we show that the monocytic cell line U937 can directly adhere to BST2 extracellular domain-coated tissue culture wells. These results provide experimental evidence to support a novel role for BST2 in the interaction between human monocyte and IFN-γ-stimulated endothelium.