Adiponectin, an adipokine secreted specifically from adipose tissue, has plurifunctions including antidiabetic, antiatherosclerotic, and antiinflammatory functions. Recently, platelet activation and the subsequent local inflammation have been implicated in progression of atherosclerosis. The aim of the study is to examine the interrelation among plasma adiponectin levels, platelet activation status and quantitatively determined carotid atherosclerosis. Subjects (n = 277) including 136 type 2 diabetic, 138 hypertensive, and 203 hypercholesterolemic patients participated in the study. Platelet activation was determined as percentage of polymorphonuclear cells (PMNs) or monocytes aggregated with platelets analyzed by CD41-positivity determined by whole-blood flow cytometry. PMN-platelet aggregates were significantly and positively associated with carotid atherosclerosis (intimal-medial thickness, IMT) with the interaction stronger than that of monocyte-platelet aggregates. Stepwise regression analyses revealed that PMN-platelet aggregates were the third strongest determinant of carotid IMT, with age and HbA1c stronger independent determinants. Simple and stepwise regression analyses of the factors associated with PMN-platelet aggregates revealed that HbA1c (r = 0.423), serum adiponectin levels (r = -0.289) and age (r = -0.184) were the three independent determinants. Thus, our data unveil novel link between hypoadiponectinemia and platelet activation.