A chronic consequence of diabetes mellitus (DM), diabetic nephropathy (DN) typically advances to end-stage renal disease (ESRD). However, the pathophysiology of DN is not fully understood. It has been revealed that several miRNAs have been considered as risk or protective factors in DN.  Inflammation is a key determining factor in the development and progression of diabetes. The aim of the current study was to investigate the association of serum miR-181a, serum, and urine IL-6, and IL- 18 with DN. miR-181a was estimated by RT- qRT-PCR, IL-6, and IL- 18 were estimated by enzyme-linked immunosorbent assay (ELISA). 120 patients were divided into three groups; Group 1: 40 DM type 2 without DN, group 2: 40 DM type 2 with diabetic DN, and group 3: 40 control patients. Group 2 was further subdivided into 20 macroalbuminuria and 20 microalbuminuria patients. When DN patients were compared to other groups, their levels of miR-181a, IL-6, and IL-18 increased significantly. Higher levels of miR-181a in patients with macroalbuminuria than patients with microalbuminuria in DN group. Serum miR-181a significantly positively correlated with fasting insulin, fasting glucose, HOMA IR, ACR, serum IL-6 and BMI in DN group. The ROC curve analysis revealed high significant specificity and sensitivity of serum miR-181a, serum, and urine IL-6, and IL-18 suggesting their possible utility for the primary diagnosis of DN in DM. It is concluded that miR-181a may prove to be a valuable biomarker for DN prognostic and diagnostic applications