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<h4>Background</h4> Chronic low-grade inflammation is considered one of the major mechanisms for the progression of diabetic kidney disease. We investigated the prognostic value of circulating soluble tumor necrosis factor receptor 2 (sTNFR2) for early nephropathy in patients with type 2 diabetes. <h4>Materials and methods</h4> A total of 364 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 were followed up for a median of 4 years. Renal outcomes were defined as a composite of either or both a >30% decline in the eGFR and/or albuminuria stage progression determined with consecutive tests. <h4>Results</h4> Seventy-three patients developed renal composite events. Serum concentrations of sTNFR2 were strongly associated with the risk of renal function decline and progressive changes in albuminuria. Through a receiver operating characteristic curve analysis, a serum sTNFR2 level of 1.608 ng/mL was adopted as the discriminator value for predicting renal outcomes (area under the curve 0.63, 95% confidence interval 0.57–0.70, p < 0.001), yielding a sensitivity of 75.3% and a specificity of 51.2%. The association of sTNFR2 levels ≥1.608 ng/mL to renal outcomes was significant after adjusting for relevant variables (hazard ratio 2.27, 95% confidence interval 1.23–4.20, p = 0.009) and remained consistent across subgroups stratified by age, sex, systolic blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system blockers. <h4>Conclusions</h4> Higher circulating levels of sTNFR2 are independently associated with an eGFR decline and progressive albuminuria in patients with type 2 diabetes.