Background <p>Diabetic nephropathy is a common complication of uncontrolled hyperglycemia in diabetic patients, usually leading to renal failure. Therefore, establishing rapid, easy-to-use diagnostic biomarkers is essential for effective monitoring of patients. Serum cytokine levels might be a potential option for this purpose.</p> Objectives <p>In this study, we aimed to compare the serum levels of soluble TNF Receptor 1 (sTNF-R1), Transforming Growth Factor beta (TGF-β), and amyloid A (SAA) between patients without nephropathy and healthy individuals, and to assess their associations with clinical indices.</p> Methods <p>The serum levels of sTNF-R1, TGF-β, and SAA were measured by ELISA in 60 patients with DN, 60 diabetic patients without nephropathy, and 60 healthy individuals, in association with clinical findings.</p> Results <p>sTNF-R1 was elevated in DN patients compared to the healthy subjects (<i>p</i>-value 0.002). SAA levels were significantly different between the three groups, with the highest amounts in DN. However, TGF-β levels were comparable across groups. SAA showed a significant correlation with clinical findings including creatinine levels (<i>p</i>-value 0.007), estimated glomerular filtration rate (eGFR) (<i>p</i>-value 0.004), and urine albumin-creatinine ratio (UACR) (<i>p</i>-value 0.07) with AUC of 0.85.</p> Conclusion <p>Serum levels of sTNF-R1 and amyloid A increased in patients with diabetic nephropathy and showed a correlation with clinical findings. TNF-R1 did not show a significant elevation in diabetic patients without nephropathy, suggesting it as a potential biomarker for established disease. In contrast, SAA levels were elevated in both patient groups compared to healthy controls, demonstrating a higher prognostic value for clinical and subclinical diabetic nephropathy. Moreover, TGF-β was neither elevated nor correlated with renal function in DN patients.</p>