This study investigates the underlying mechansisms of monocyte adhesion to both short term (IL-1β, 4 hr) and long term (IL-4, 24 hr) activated endothelial cells. At a wall shear stress of 2 dynes/cm2, monocytes appear to use multiple pathways for primary and secondary adhesion to IL-1β, 4 hr stimulated endothelial cells. However, on IL-4 24 hr stimulated HUVECs, VLA-4/VCAM-1 was the dominant mechanism for monocyte adhesion. Upon additional histamine exposure of IL-4, 24 hr treated endothelial cells, both P-selectin and VLA-4 were involved and had to blocked simultaneously to abolish monocyte adhesion. A combination of IL-1+IL-4 (24 hr) treatment resulted in a complete loss of the primary adhesive mechanism under flow conditions whereas secondary adhesion remained intact as indicated by static experiments.