Background: Diabetic nephropathy (DN) is a significant complication of type 2 diabetes mellitus (T2DM), resulting in end-stage renal failure and chronic kidney disease. Current diagnostic methods, primarily based on microalbuminuria, have limitations, as renal function may decline before its onset. Chromogranin A (CgA), a neuroendocrine protein cleared by the kidney, was proposed as a potential early biomarker for DN. Objective: This research evaluates serum CgA levels in relation to different stages of albuminuria and its diagnostic utility in initial identification of DN. Subjects and methods: This case-control research comprised 80 patients split up into 4 groups: T2DM with normoalbuminuria (n=20), microalbuminuria (n=20), macroalbuminuria (n=20), and healthy controls (n=20). Serum CgA was determined utilizing enzyme-linked immunosorbent assay (ELISA). Other parameters comprised eGFR, serum creatinine, lipid profile, HbA1c, and fasting plasma glucose (FPG). Diagnostic accuracy was ascertained utilizing receiver operating characteristic (ROC) curve analysis. Results: Serum CgA levels were significantly elevated in macroalbuminuria (1606.8 ± 868.9 ng/L), microalbuminuria (706.7 ± 213.2 ng/L), and normoalbuminuria (557.6 ± 94.1 ng/L) compared to controls (500.5 ± 56.3 ng/L) (p < 0.001). CgA positively connected to albumin-creatinine ratio (r = 0.507, p < 0.001) and negatively with eGFR (r = -0.317, p=0.005). ROC analysis showed CgA had a sensitivity of 85.0% and specificity of 75.0% at a cutoff of 610 ng/L for detecting albuminuria (AUC=0.853, p < 0.001). Conclusions: Serum CgA is a promising biomarker for initial identification of DN, showing significant associations with albuminuria and renal function decline. Incorporating CgA into clinical practice may enhance early diagnosis and intervention in DN.