Objective- Visfatin is as a novel adipocytokine with proinflammatory properties, which has been linked to cardiovascular diseases including atherosclerosis. However, the biological roles of visfatin in the pathogenesis of atherosclerosis remain unknown. Therefore, we evaluated the effects of short term visfatin exposure on monocyte/macrophages differentiation, an initial step in atherogenesis. Methods and Results- Using the monocytic cell line THP-1 treated with PMA, the effect of visfatin on monocyte differentiation was determined by changes of cell adhesion, morphology. In the presence of visfatin, PMA-induced THP-1 cells became more adherent. Immunofluorescence microscopy revealed that short-time incubation of visfatin induces F-actin rich membrane protrusion formation and spreading, indicating that visfatin alters morphology and cytoskeletal organization. In addition, clustering of CD11b integrin, mediator of monocyte adhesion, was increased in visfatin-treated cells, which was localized to the protruding structure. Furthermore, we also found that visfatin enhances CD11b integrin expression to greater levels than that induced by PMA at 48h and 60h. Blocking with anti-CD11b diminished visfatin-enhanced cell adhesion. The pretreatment with pp2, Src family kinase inhibitor, completely suppressed the cell adhesion and clustering of CD11b integrin. Conclusions- Taken together, these data suggest that visfatin enhance CD11b-mediated cell adhesion via actin reorganization and this may be regulated by CD11b avidity and Src family kinase activity, providing a novel pro-atherogenic effect of visfatin. Key word: Visfatin, CD11b, cell adhesion, Src family kinase, differentiation