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Recently, leptin has been suggested as a possible cause of atherosclerotic disease. In the present study, we have investigated in postmenopausal women (n=60; age: 52±13) the relationship between circulating levels of leptin, oxidized LDL (Ox-LDL) and other biochemical and anthropometric variables of atherosclerotic risk. In addition, we have evaluated soluble thrombomodulin (sTM) as a marker of endothelial damage. An additional study was conducted in a subgroup of obese subjects to determine the short-term effects of weight loss on selected variables. Ox-LDL showed a positive correlation with leptin circulating levels (r=0.65, P<0.0001). A significant association was also found between Ox-LDL and body mass index (r=0.69, P<0.0001), waist-to-hip ratio (r=0.50, P<0.0001), insulin levels (r=0.65, P<0.0001), HOMA index (r=0.55, P<0.0001) and sTM (r=0.74, P<0.0001) levels. After multivariate regression analysis leptin was still related to Ox-LDL levels (P=0.007). In obese women who completed the program of weight reduction, leptin changes persisted as a significant predictor of plasma changes in Ox-LDL levels. These findings suggested a novel link between leptin and Ox-LDL, possibly involved in atherosclerotic disease. [Copyright &y& Elsevier]