Abstract: Objective To investigate the relationship of serum leptin and adiponectin levels with insulin resistance(IR) in the nondiabetic first-degree relatives of type 2 diabetic mellitus (T2DM) through measuring serum leptin and adiponetin levels. Methods 153 normal glucose tolerance subjects were enrolled, including 41 control without T2DM family history, 36 patients with paternal T2DM history,45 patients with maternal T2DM history, 31 patients with parental T2DM history. The levels of blood glucose, lipid, insulin, leptin, and adiponectin were measured in four groups. Results The 3 subgroups of the first-relatives of type 2 diabetes had the higher levels of serum leptin [(11±6),(10±5),(11±9)μg/L] than control(8±6)μg/L (P<0.05), higher insulin resistance index [(3.0±1.4),(2.9±1.5),(3.3±1.5)] than control(2.0±0.8)(P<0.05), and lower serum adiponectin [(11±6),(10±6),(12±8) g/L] than control (17±11 g/L) (P<0.05).The other metabolic indexes were in no difference among the groups with family history of type 2 diabetes. BMI, leptin, and adiponectin were independent risk factors for HOMA-IR. Conclusion The degree of insulin resistance in first-degree relatives of type 2 diabetes was significantly higher than in control. Adiponectin and leptin may affect the IR of first-degree relatives of type 2 diabetes.