Diabetic nephropathy is traditionally viewed as non immune disease, emerging evidence suggests that inflammatory mechanisms play an important role in disease pathogenesis and progression. Indeed, the decline of renal function in diabetic patients with proteinuria is positively associated with tubulointerstitial inflammation .Inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy. Numerous experimental and clinical studies have shown the participation of different inflammatory molecules and pathways in the pathophysiology of this complication.Among all members of toll-like receptors, it was found that TLR2 and 4 activation in the pathogenesis of Diabetes mellitus and its complications are significant. Recent findings have shown increased TLR2/4 expression, signaling, ligands, and functional activation in diabetic subjects compared with controls, which is further accentuated in monocytes of diabetes mellitus with microvascular complications (mainly nephropathy).