Introduction: The intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in inflammation and linkage between monocytes and endothelium. LDL-induced ICAM-1 expression may include the possibility of an atherogenic stimulation due to a binding between lipoprotein and ICAM-1. To evaluate of this hypothesis, the present study investigated the effect of sICAM-1 on susceptibility of LDL and HDL to oxidation and Paraoxonase-1 (PON-1) activity. Materials and Methods: LDL and HDL were purified from serum via ultracentrifugation and 25 and 100 µg-protein/ml of LDL and HDL, in the presence of sICAM-1 (0, 2, 5 ng/ml), were exposed to oxidative stress (5 µM copper) and assayed through monitoring of formation of conjugated dienes using a spectrophotometer. Electrophoresis was performed to determine the mobility of incubated-lipoproteins with sICAM-1. The activity of PON-1 was assayed in the presence of of sICAM-1. Results: In presence of different concentrations of sICAM-1, Vmax increased significantly (P<0.05), while electrophoretic mobility of LDL decreased (↓ 25%). PON-1 activity increased at low levels of sICAM-1 but decreased at higher levels (P<0.05 P<0.005). Conclusion: The results indicate that sICAM-1 in dosages over than 2  ng/ml affects some kinetical parameters of LDL oxidation and PON-1 activity that can be interpreted as a positive stimulus in atherogenesis. Overall the results may support the hypothesis of a lipoprotein-mediated role for ICAM-1 in atherogenesis. of