Objective To investigate the relationship between gene polymorphism of transcripion factor 7-like 2 (TCF7L2) at positions rs290487, rs11196205, rs11196218 and gestational diabetes mellitus (GDM) in Chinese women.Methods In 1140 unrelated pregnant Northern Chinese women (335 women with GDM, 158 gestational cases with impaired glucose tolerance and 647 pregnant non-diabetic controls) ,three single nucleotide polymorphisms (rs290487, rs11196205, and rs11196218) in the TCF7L2 gene were genotyped using ligase detection reaction (LDR).In the present study, cases with GDM and impaired glucose tolerance (IGT) were indistinguishable clinically and biochemically, and were combined into case group.Results The frequency of C allele of rs290487 was 41.6% in case group, being significantly higher than that in control group (36.3%, P=0.012).There was significant difference in the frequency of CC genotype between case group and control group (18.7% vs 14.0%, P=0.033).Compared with T allele carriers, CC genotype carriers had a 1.418-fold increased risk of GDM (95% CI 1.028-1.955).After adjusting for age, body mass index, family history of diabetes,systolic blood pressure,and diastolic blood pressure, pregnant women with CC genotype carriers of rs290487 were more prone to hyperglycemia compared with the T allele carriers (OR 1.518, 95% CI 1.064-2.166).Conclusions The TCF7L2 rs290487 variant may contribute to the genetic predisposition to GDM.CC genotype is likely to be associated with an increased risk of GDM in the pregnant Chinese women.