Background: Diabetic nephropathy is the most prevalent cause for endstagerenal disease in the United States and the Western World.In this disease, tubular injury and progressive interstitial fibrosiscontribute significantly to renal failure and predict progression to end-stagerenal disease. In early diabetic renal injury, there is podocyte drop-out which is thought to cause glomerular proteinuria and subsequent diabeticglomerular injury.Different inflammatory molecules including pro-inflammatory cytokineshave been proposed as critical factors in the development of microvasculardiabetic complications including nephropathy.Interleukin 10 (IL-10) polymorphic variants are linked with cytokineproduction and are involved in many chronic inflammatory diseases,including type 2 diabetes mellitus .Aim of work: Analysis of IL-10 gene polymorphisms and study theirpossible association with IL-10 gene expression involved in the progressionof diabetic nephropathy in type 2 diabetes mellitus .Methods: For all subjects, IL-10 plasma levels (by ELISA), IL-10 – (-592)gene polymorphism (by PCR) were investigated.Results: we found that the highest levels of IL-10 were in diabetic patients withnephropathy followed by diabetic patients without nephropathy with the lowestlevels in normal healthy subjects. Also we found that there is an increase in thefrequency of IL-10-(-592) AA genotype in diabetic nephropathy patients with asignificant increase in A allele distribution in them compared to diabetic patientswithout nephropathy and healthy control subjects.Conclusion: IL-10 and its gene polymorphism play an important role in theprogression of diabetic nephropathy.