The main goal of this study was to compare the expression of Zinc-alpha2-glycoprotein (ZAG), a recently described adipokine, in obese and lean subjects. ZAG expression was determined by Real-time PCR analysis in subcutaneous abdominal adipose tissue of eighteen young men, 9 lean (BMI = 23.1 +/- 0.4 kg/m2) and 9 obese (34.7 +/- 1.2 kg/m2) with a similar habitual dietary intake of fat and physical activity, which were assessed by validated methods. Our data revealed that ZAG gene was downregulated (-70%; p < 0.05) in subcutaneous adipose tissue of obese compared to lean subjects. Moreover, statistically significant positive correlations between ZAG gene expression and serum adiponectin (r = 0.89; p < 0.01) and a negative correlation with the plasma levels of leptin (r = -0.82; p < 0.05) and waist circumference (r = -0.64; p < 0.05) were found in obese subjects. Our data suggest that this novel adipokine could play a role in human susceptibility to obesity related disorders and that upregulation of ZAG could be a promising therapeutic target for metabolic syndrome treatment.