The role of resistin in obesity and insulin resistance in humans is controversial. Therefore, resistin protein was quantitated by ELISA in serum of 27 lean [13 women/14 men, body mass index (BMI) 21.7 ± 0.4 kg/m², age 33 ± 2 yr] and 50 obese (37 women/13 men, BMI 49.8 ± 1.5 kg/m², age 47 ± 1 yr) subjects. There was more serum resistin protein in the obese (mean ± sem: 5.3 ± 0.4 ng/ml; range 1.8–17.9) than lean subjects (3.6 ± 0.4 ng/ml; range 1.5–9.9; P = 0.001). The elevation of serum resistin in obese humans was confirmed by Western blot as was expression of resistin protein in human adipose tissue and isolated adipocytes. There was a significant positive correlation between resistin and BMI (r = 0.37; P = 0.002). Multiple regression analysis with predictors BMI and resistin explained 25% of the variance in homeostasis model assessment of insulin resistance score. BMI was a significant predictor of insulin resistance (P = 0.0002), but resistin adjusted for BMI was not (P = 0.11). The data demonstrate that resistin protein is present in human adipose tissue and blood, and that there is significantly more resistin in the serum of obese subjects. Serum resistin is not a significant predictor of insulin resistance in humans.