Objective: Human resistin has been stated to influence preadipocyte cell numbers and to stimulate adipocyte triglyceride lipolysis in vivo and in vitro. However, its role in human obesity remains unclear. Design: Cross-sectional study for comparisons of lean and obese subjects, and subsequent longitudinal 4-month weight loss intervention study in obese subjects. Subjects: Healthy subjects, lean (n ¼ 20, BMIo25) and overweight (n ¼ 43, BMIX25). Measurements: Serum resistin, body weight, body fat, waist-to-hip ratio, as well as markers of insulin resistance and lipid metabolism at baseline and after 4 months of intervention. Results: Serum resistin was positively correlated to HOMA-IR (partial r ¼ 0.288; P ¼ 0.055), serum fructosamines (partial r ¼ 0.280; P ¼ 0.062), serum NEFA (partial r ¼ 0.276; P ¼ 0.066) and negatively to age (partial r ¼ À0.349; P ¼ 0.019) and serum apolipoprotein A-1 (partial r ¼ À0.363; P ¼ 0.014). During the intervention, serum resistin increased significantly (Po0.001). The increase was inversely related to changes in waist-to-hip ratio (P ¼ 0.025) and positively to serum apolipoprotein B (P ¼ 0.011). In males only, the increase in resistin during weight loss was predicted by total serum cholesterol at baseline (r ¼ 0.703, P ¼ 0.007). No relation was observed between changes in resistin and changes in HOMA-IR. Conclusion: The present study indicates an association between serum resistin and markers of abdominal fat distribution as well as the regulation of lipid metabolism. However, human resistin is unlikely to play an independent role in the regulation of glucose metabolism.