Background <p>Diabetes mellitus (DM) is a significant global health issue, marked by chronic hyperglycemia and correlated with increased morbidity and mortality. Irisin, is an adipo_ myokine, has a positive effect on lipid metabolism and glucose.</p> Aim <p>This research aims to examine the relationship among serum irisin level in cases with type II diabetes and development of diabetic nephropathy.</p> Methods <p>This cross-sectional study at Assiut University Hospital included 100 participants over 40&#xa0;years old with diabetic nephropathy and type 2 diabetes. Participants have been divided into a patient group 75 individuals,subdivided into (25 patients with type II diabetes,25 patients with CKD,25 patients with diabetic nephropathy) and a control group (25 healthy individuals). Comprehensive data collection involved medical history, physical examinations, laboratory tests (CBC, kidney and liver function, glucose, lipid profiles), urinary analysis, and serum irisin measurement via ELISA.</p> Results <p>Serum irisin levels were significantly various among groups lower in cases (had a mean of 33.02 ± 10.41) in comparison to control group 55.28 ± 31.39 (<i>p</i> &lt; 0.001). Early-stage CKD patients had higher serum irisin than late-stage CKD patients (55.20 ± 13.6 vs. 28.95 ± 9.78, <i>p</i> &lt; 0.001).</p> Conclusion <p>The study demonstrates a significant link among diabetic nephropathy and serum irisin levels in (T2DM) cases. Lower irisin levels correlate with higher blood glucose, suggesting its potential as a biomarker for early detection of diabetes and its related complications.</p>