The aim of the study was to investigate the association between single nucleotide polymorphisms (SNPs), rs1861612 of delta/notch-like Epidermal Growth Factor (EGF)-related receptor (DNER) and rs1884190 in the Delta-like 1 ligand (DLL1) gene and type 2 diabetes mellitus (T2DM) susceptibility in a Chinese Han population. DNER rs1861612 and DLL1 rs1884190 polymorphisms were genotyped in patients with T2DM and age- and sex-matched T2DM-free controls from a Chinese Han population. A total of 298 patients with T2DM and 500 controls were enrolled in this study. We found that TC and TT genotypes of rs1861612 and variant T were associated with a significantly increased risk of T2DM. In contrast, the AG and AA genotypes of rs1884190 were not significantly associated with the risk of T2DM, even after further stratification analysis based on age or sex. Our results showed that DNER rs1861612 C to T change and variant T genotype may contribute to T2DM in a Chinese Han population.