Abstract： Objective A recent study has shown the association between a sulfonylurea receptor gene 1 (SUR1) variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group,supporting the hypothesis that the primary insulin hypersecretion may be an antecedent of type 2 diabetes.Methods To test this hypothesis in Chinese population,we studied the allele and genotype distribution of the polymorphism at -3 position of intron 24 in SUR1 by PCR RFLP technique in 206 unrelated normal glucose tolerant subjects with strong family history of type 2 diabetes (group A) and 110 normal individuals without family history of diabetes (group B).Results The frequency of “-3c” allele and “-3cc” genotype of intron 24 in group A was significantly higher than that in group B (64% vs 54%, P =0 004 and 38% vs 24%, P =0.002 respectively).Moreover,in group A, those carrying “cc” genetype had a higher BMI (27 27±6 37 vs 24.99±3.43kg/m 2, P <0.05;27 27±6 37 vs 25.28±2.78kg/m 2, P <0.05),fasting insulin (15 52±10 72 vs 9.27±5.03U/ml, P <0.01;15 52±10 72 vs 10.79±7.80U/ml, P <0.05) and 2h insulin levels (76.41±54 02 vs 55.43±49.60U/ml, P <0.01;76 41±54 02 vs 55.71±40.39, P <0.05) as well as lower insulin sensitivity [HOMA(R i]: 4.00±3.09 vs 2.79±1.32, P <0.01; 4.00±3.09 vs 2.82±2.94, P <0.01) as compared with that in carriers of other genotypes (“ct” and “tt”).Conclusion This study suggested the possibility that the defect in SUR1 gene might contribute to the insulin hypersecretion which might be the cause of subsequent increased body weight and decreased insulin sensitivity.