The aim of our study was to evaluate the relationship of adiponectin to soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular cell adhesion molecule-1 (sICAM-1) in patients with cardiovascular disease or dyslipidemia. Two hundred and sixty-four patients (134 men/130 women, mean age 43.8+/-14.8/46.0+/-14.9 years) of Lipid Center, University Hospital Olomouc, off hypolipidemic therapy for at least 6 weeks, participated in the study. In multiple regression analysis, adiponectin was independently positively associated with serum HDL-cholesterol (p<0.0001) and sVCAM-1 (p<0.0001), female gender (p<0.0001) and negatively with hs-CRP (p=0.014). Serum concentration of adiponectin and sICAM-1 did not correlate but sICAM-1 was independently, positively associated with sVCAM-1 (p<0.0001) and negatively with markers of insulin resistance and inflammation, namely atherogenic index log[triglycerides/HDL-cholesterol] (p<0.0001), hs-CRP (p<0.001) and HOMA (p<0.05). Positive association of adiponectin with HDL-C and negative association with hs-CRP indicate anti-atherogenic properties of adiponectin. The finding of the positive association of adiponectin with sVCAM-1 in patients at risk is unexpected. We hypothesize that adiponectin may be involved (directly or indirectly) in shedding of ectodomains of VCAM-1 from endothelial surface and in this way down-regulates their effects. This process may be protective in the initial stages of atherosclerosis.