Objective To investigate the relationship between the polymorphism of site rs228648 in urotensin Ⅱ gene and the genetic susceptibility to gestational diabetes mellitus in northern Chinese women. Methods Genotyping was conducted to investigate the polymorphism of site rs228648 (G—A) in urotensin Ⅱgene among 70 unrelated gestational diabetes mellitus(GDM) subjects and 70 normal controls. DNA samples isolated from leucocyte of the control and study groups were analyzed for single-nucleotide polymorphisms of the urotensin Ⅱ gene at positions rs228648 using polymerase chain reaction and restriction analysis. Results (1)The distribution of genotype frequencies of site rs228648 accorded with Hardy-Weinberg′s equation law, being colony representative.(2)The frequency of G allele of site rs228648 was 70.7% in GDM group, significantly higher than that in the control group (57.9%, P0.05). (3) Women in control group were more likely to be homozygous for the allele A of site rs228648 than women with GDM. The frequency of A/A genotype of rs228648 was negatively correlated with GDM group. By the logistic procedure, after adjustment by age and gestational weeks, the odds ratio was 0.312 , and Wald Confidence Limites were 0.108 to 0.900 (P= 0.031). Conclusion Urotensin Ⅱ gene may contribute to the genetic susceptibility to gestational diabetes mellitus in northern Chinese population. G allele of site rs228648 is related to GDM possibly, and that homozygosis A of site rs228648 is likely to be an important protecting factor for GDM.