Obese individuals have hyperleptinemia and hypozincemia. Moreover, leptin and zinc have circadian changes in circulating concentrations. We investigated their possible interaction and examined whether a difference existed between obese men and their lean controls. The results indicated the pattern of circadian change in plasma zinc and leptin did not markedly differ between the obese subjects and the lean controls. However, the obese had higher leptin and lower zinc plasma values at each sampling time than did the lean controls. Because an inverse correlation was found in plasma values between zinc and leptin (r=-0.51, p=0.012), we further determined the role zinc might play in leptin production by human subcutaneous adipose tissue from female donors. The in vitro study showed that zinc treatment (0.2 mmol/L) significantly increased leptin production (142%), however, this increment did not surpass that by insulin (10 nmol/L). The data of this study suggest an interactive connection between zinc and leptin.