To explore the significance of Hey, the gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677 T and cystathionine beta- synthase (CBS844) ins68 in type 2 diabetes mellitus (DM) with coronary heart disease (CHD) in China. Methods We selected 70 patients with type 2 DM and CHD, 71 type 2 diabetes patients, and 85 controls in Han nationality from northern China. Hey levels were measured by fluorescence polarization immunoassay (FPIA) and the plasma folate and vitamin B12 levels by microparticle enzyme immunoassay (MEIA). The gene polymorphisms of the MTHFR C677 T were determined by PCR- RFLP assay and the gene polymorphisms of the CBS 844ins68 were determined by PCR assay. The plasma Hey levels in DM with CHD group (14.8 micromol/L) were significantly higher than in DM group (11.1 micromol/L) and control group (11.2 micromol/L), (P < 0.01). The levels of plasma folate and Vitamin B12 in DM with CHD group were significantly lower than in DM group and control group, (P < 0.05). The T allelic frequency of MTHFR in DM and CHD group was significantly higher than that in DM group and controls (45% vs 26.8%, 31.2%, P < 0.01). There were no significant differences in the frequencies of CBS 844ins68 polymorphism among 3 groups (P > 0.05). Logistic-regression analysis indicated that the OR of HHcy was 4.547 (95% CI 1.97-10.496) (P < 0.01), the OR of MTHFR 677 with T (including MTHFR CT genotype and Tr genotype)was 2.369 (95% CI 1.160-4.841), (P = 0.018), and the OR of CBS 844ins68 was 0.384 (95% CI 0.033-4.423), (P = 0.443). Hyperhomocysteinemia and MTHFR with T allele might be the risk factors for DM with CHD in northern Chinese Han population.