Abstract： Objective To observe the role of the mild changes in hepatic nuclear factor (HNF)-1α gene in the pathogenesis of type 2 diabetes mellitus. Methods With PCR, denatured gradient gel electrophoresis and DNA sequencing,the genomic DNAs from the blood of type 2 diabetic patients and normal control were analyzed to find the changes in HNF-1α gene. These changes were added up in-groups and compared with plasma insulin concentration. Results Code 459 CTG changed to TTC,codes 489 AGC changed to AAC in the 7th exon;no 7G changed to A in the 7th intron. The 3 point changes were of one kind of polymorphism. Its frequency to normal genotype was 61: 39 in normal control, 56: 44 in type 2 diabetes mellitus. Homozygotes of the polymorphism in the group of type 2 diabetes mellitus had slightly lower plasma insulin concentration, but t-test result was P<0.05 only between their highest plasma insulin concentration after glucose-stimulating and that of normal genotypes. Conclusion The polymorphism found might lower the transcription of insulin gene, leading to insulin secretion decrease. It might play a role in the pathogenesis of type 2 diabetes mellitus.