T-cadherin (CDH13) is an adiponectin receptor. Genome-wide association studies have identified the CDH13 gene as one of the most important candidate genes in influencing plasma adiponectin levels. Several studies recently reported single-nucleotide polymorphisms (SNPs) in CDH13 gene were associated with T2DM. The purpose of this study was to investigate the association between T2DM and 6 SNPs (rs11646213, rs12596316, rs3865188, rs12444338, rs12051272, and rs7195409) in the CDH13 gene in a Han Chinese population. A total of 674 subjects with T2DM and 588 subjects without T2DM were genotyped using the TaqMan method. Our data showed that there was an association between the SNP-rs12596316 genotype and T2DM (P < .05). Moreover, an overdominant model of inheritance showed that being an rs12596316AG heterozygote increased the risk of T2DM (P = .0041, odds ratio = 1.39; 95% confidence interval 1.11–1.73) in comparison with rs12596316AA-GG. The other 5 SNPs did not show associations with T2DM, either in the allele levels or in different inheritance models. The haplotype analysis showed that there were no associations between any haplotypes and T2DM. Our results revealed that genetic variations in the CDH13 gene were associated with T2DM susceptibility in a Han Chinese population. These results highlight the need to study the functional effects of these CDH13 gene variants in relation to the risk of developing T2DM.