Genetic variation has been implicated to play some roles in the development of diabetic nephropathy. This prospective study examined if adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPs) as well as clinical risk factors predict nephropathy progression in type 2 diabetes. A total of 571 subjects who participated in the DMIDS cohort and free of nephropathy at baseline were followed up for average 5 years. Urinary albumin-to-creatinine ratio (ACR)30mg/g in two consecutive urine tests were used to define nephropathy progression (n=146). Five ADIPOQ tag SNPs were genotyped (rs1501299, rs182052 , rs16861194, rs3821799, and rs7627128). Result showed that the distributions of SNP genotype frequencies were similar between progression and non-progression groups (p>0.05), and all SNPs were not statistically associated with nephropathy progression. In multivariate Cox proportional hazard model, risk factors including HbA1C8% (HR=1.58, p=0.008) and education<6 years (HR=1.64, p=0.011) significantly predicted greater risk of nephropathy, and male gender (HR=1.35, p=0.096) and DM duration 10 years (HR=1.40, p=0.097) were marginally correlated. In conclusion, our data showed that ADIPOQ SNPs are not independent risk factors for incident nephropathy, but subjects with clinical characters such as low education and high HbA1C may appear to be high risk groups for nephropathy in type 2 diabetes.