Single-nucleotide polymorphisms (SNPs) of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus (T2DM), but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs of ADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects. rs16861194 (-11426 A>G) in the putative promoter of ADIPOQ was associated with T2DM (P = 0.007; OR = 1.29, 95%CI 1.08-1.55). None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.