Objective: To study the allelic and genotypic frequency distribution of RETN—420C/G single nucleotide polymorphisms (SNPs) and its relationship with type 2 diabetes mellitus (T2DM) complicated with macroangiopathy in Han population of northeast China. Methods: The genotypes and their frequencies of a total of 180 cases, including 60 cases of T2DM complicated with macroangiopathy, 60 cases of simple T2DM and 60 cases of normal control (ND), were measured by PCR—RFLP. Results: The allelic frequencies and simple CC/GC + GG genotype in T2DM complicated with macroangiopathy group were significant different compared with ND group (P < 0.01). The allelic frequencies and CC/GC + GG genotype in T2DM complicated with macroangiopathy group were significant different compared with T2DM group (P < 0.05). The GC + GG genotype in T2DM complicated with macroangiopathy group was significantly higher than that in T2DM group (P < 0.05). Conclusion: The RETN—420C/G polymorphism has a correlation with the occurrence of T2DM complicated with macroangiopathy in Han population of northeast China.