Substantial evidence suggests that type 2 diabetes mellitus (T2DM) is a multi-factorial disease with a strong genetic component. A list of genetic susceptibility loci in populations of European and Asian ancestry has been established in the literature. Little is known on the inter-ethnic contribution of such established functional polymorphic variants. We performed a case-control study to explore the genetic susceptibility of 16 selected T2DM-related SNPs in a cohort of 102 Uyghur objects (51 cases and 51 controls). Three of the 16 SNPs showed significant association with T2DM in the Uyghur population. There were significant differences between the T2DM and control groups in frequencies of the risk allelic distributions of rs7754840 (CDKAL1) (p=0.014), rs864745 (JAZF1) (p=0.032), and rs35767 (IGF1) (p=0.044). Carriers of rs7754840-C, rs35767-A, and rs864745-C risk alleles had a 2.32-fold [OR (95% CI): 1.19-4.54], 2.06-fold [OR (95% CI): 1.02-4.17], 0.48-fold [OR (95% CI): 0.24-0.94] increased risk for T2DM, respectively. The cumulative risk allelic scores of these 16 SNPs differed significantly between the T2DM patients and the controls [17.1±8.1 vs. 15.4±7.3; OR (95%CI): 1.27(1.07-1.50), p=0.007]. This is the first study to evaluate genomic variation at 16 SNPs in respective T2DM candidate genes for the Uyghur population compared with other ethnic groups. The SNP rs7754840 in CDKAL1, rs864745 in JAZF1, and rs35767 in IGF1 might serve as potential susceptibility loci for T2DM in Uyghurs. We suggest a broader capture and study of the world populations, including who that are hitherto understudied, are essential for a comprehensive understanding of the genetic/genomic basis of T2DM.