Objective To explore the relationship between IRS-4 and GCKR gene polymorphism in patients with diabetic mellitus in Mudanjiang. Methods PCR-RFLP method was used to measure the polymorphism of IRS-4 and GCKR. Genotype frequency and allele frequency were analysised. Results In the analysis of IRS-4, the frequency of genotype GG, GC and CC in the Han population was 0.538, 0.404, and 0.058, respectively. The frequency of G and C allele was 0.740 and 0.260, respectively. In the control healthy population, the frequency of genotype GG, GC and CC was 0.556, 0.352 and 0.092, respectively. The frequency of G and C allele was 0.732 and 0.268, respectively. Both of the genotype frequency and allele frequency were similar between the two populations (P0.05). In the analysis of GCKR, the frequency of genotype PP, PL and LL was 0.212, 0.596 and 0.192, respectively. The frequency of P and L allele was 0.510 and 0.490, respectively. In the healthy control population, the frequency of genotype PP, PL and LL was 0.148, 0.463 and 0.389, respectively. The frequency of P and L allele was 0.380 and 0.620, respectively. Both of the genotype frequency and allele frequency were similar between the two populations (P0.01). Conclusion Only the gene polymorphism of GCKR P446L is correlated with T2DM in the Mudanjiang Han population.