Diurnal patterns of circulating leptin concentrations are attenuated following consumption of fructose-sweetened beverages compared with glucose-sweetened beverages, likely a result of limited postprandial glucose and insulin excursions after fructose. Differences in postprandial exposure of adipose tissue to peripheral circulating fructose and glucose or in adipocyte metabolism of the two sugars may also be involved. Thus, we compared plasma leptin concentrations following 6-hour intravenous infusions of saline, glucose or fructose (15 mg/kg/min) in overnight-fasted adult rhesus monkeys (n=9). Despite increases of plasma fructose from undetectable levels to 2 mM during fructose infusion, plasma leptin concentrations did not increase, and the change of insulin was only 10% of that seen during glucose infusion. During glucose infusion, plasma leptin was significantly increased above baseline concentrations by 240 minutes and increased steadily until the final 480 minute timepoint ( leptin = +2.5 ± 0.9 ng/ml, p<0.001 vs. saline; % leptin = +55 ± 16%; p< 0.005 vs. saline). Substantial anaerobic metabolism of fructose was suggested by a large increase of steady-state plasma lactate ( lactate 1.64 ± 0.15 mM from baseline), which was significantly greater than that during glucose (+0.53 ± 0.14 mM) or saline (-0.51 ± 0.14 mM) infusions (p<0.001). Therefore, increased adipose exposure to fructose and an active whole-body anaerobic fructose metabolism are not sufficient to increase circulating leptin levels in rhesus monkeys. Thus, additional factors (i.e., limited post-fructose insulin excursions and/or hexose-specific differences in adipocyte metabolism) are likely to underlie disparate effects of fructose and glucose to increase circulating leptin concentrations.