Adiponectin is an adipokine multipeptide hormone with insulin-sensitizing; anti-atherosclerotic; and anti-inflammatory properties. Chronic kidney disease (CKD) may be associated with low adiponectin. The adiponectin geneADIPOQis thought to be the only major gene responsible for plasma adiponectin levels; which are associated with diabetes and diabetic nephropathy. The purpose of this study was to investigate the association betweenADIPOQpolymorphism and CKD. In addition; the combined effects ofADIPOQpolymorphism and diabetes and levels of total urinary arsenic and blood cadmium on CKD were also explored. This study included 215 CKD patients and 423 age–sex matched controls. TheADIPOQpolymorphisms were determined using the Agena Bioscience Mass ARRAY System. The levels of blood cadmium and urinary arsenic species were measured. TheADIPOQrs182052 GA/AA genotype had a marginally lower odds ratio (OR) for CKD than the GG genotype. The OR (95% confidence interval; CI) was 16.33 (5.72–46.66) of CKD in subjects carrying theADIPOQrs182052 GG genotype and diabetes compared to non-diabetes subjects carrying theADIPOQrs182052 GA/AA genotype; the interaction term hadp= 0.015; and the synergy index was 6.64 (1.81–24.36) after multivariate adjustment. A significant interaction of diabetes andADIPOQrs1501299 risk genotype increased the OR of CKD after multivariate adjustment with a synergy index of 0.31 (0.11–0.86) and a multiplicative interaction withp= 0.001. These results suggest thatADIPOQrs182052 and rs1501299 risk genotypes may significantly modify the association between diabetes and CKD but not the association between total urinary arsenic and blood cadmium and CKD.