Early reports suggested that resistin is associated with obesity and insulin resistance in rodents. However, subsequent studies have not supported these findings. To our knowledge, the present study is the first assessment in human subjects of serum resistin and insulin sensitivity by the insulin clamp technique. Thirty-eight nonobese subjects [age, 23 +/- 4 yr; body mass index (BMI), 25.4 +/- 4.3 kg/m(2)], 12 obese subjects (age, 54 +/- 8 yr; BMI, 33.0 +/- 2.5 kg/m(2)), and 22 obese subjects with type 2 diabetes (age, 59 +/- 7 yr; BMI, 34.0 +/- 2.4 kg/m(2)) were studied. Serum resistin concentrations were not different among nonobese (4.1 +/- 1.7 ng/ml), obese (4.2 +/- 1.6 ng/ml), and obese diabetic subjects (3.7 +/- 1.2 ng/ml), and were not significantly correlated to glucose disposal rate during a hyperinsulinemic glucose clamp across groups. Serum resistin was, however, inversely related to insulin sensitivity in nonobese subjects only (r = -0.35; P = 0.05), although this association was lost after adjusting for percent body fat. Serum resistin was not related to percent fat, BMI, or fat cell size. A strong correlation was observed between serum resistin and resistin mRNA expression from abdominal sc adipose tissue in a separate group of obese subjects (r = 0.62; P < 0.01; n = 56). Although the exact function of resistin is unknown, we demonstrated only a weak relationship between resistin and insulin sensitivity in nonobese subjects, indicating that resistin is unlikely to be a major link between obesity and insulin resistance in humans.