Abstract: One of the main causes of end-stage renal disease worldwide is diabetic nephropathy (DN). For prompt intervention and better patient outcomes, early detection of biochemical markers linked to DN pathogenesis is essential. Objectives: the pathophysiology of diabetic nephropathy was examined in relation to inflammatory indicators (C-reactive protein [CRP], tumor necrosis factor-alpha [TNF-α]), α-Klotho, and glycemic control markers (glycated hemoglobin [HbA1c], glycated albumin, and ractopamines).. Methods: Between October 2024 and April 2025, a six-month cross-sectional study was carried out at Azadi Teaching Hospital and Kirkuk Teaching Hospital. 360 individuals were carefully split into four groups for the study: 90 patients with diabetes who did not have nephropathy, 90 patients with chronic renal disease (CRD), 90 patients with diabetic nephropathy, and 90 healthy controls. Standardized laboratory procedures were used to analyze biochemical parameters. Analysis of variance (ANOVA), post-hoc testing, correlation analysis, and multivariate regression analysis were all included in the statistical analysis. TNF-α concentrations (204.13±86.17 pg/mL vs. 32.28±13.97 pg/mL, p<0.001) and CRP levels (14.27±4.01 mg/L vs. 4.48±1.58 mg/L, p<0.001) were substantially higher in diabetic patients with nephropathy than in controls. Patients with diabetic nephropathy had significantly lower α-Klotho levels (201.27±81.42 pg/mL compared to 1173.04±271.04 pg/mL in controls, p<0.001). Glycated albumin showed a stronger association with diabetic complications (r=0.78, p<0.001) among glycemic control indicators than ractopamines (r=0.44, p<0.01) and HbA1c (r=0.61, p<0.001). The pathophysiology of diabetic nephropathy is significantly influenced by inflammatory indicators and α-Klotho deficiency. Compared to conventional glycemic indicators,