Modulation of the immune inflammatory system has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN); nevertheless, many of the underlying mechanisms are still unknown. A possible role of micro-RNA 152-3p in T2DM and DN has been suggested due to its immunomodulatory effect on the innate immunity. This case control study aimed, first, to determine the possible role of micro-RNA 152-3p in the pathogenesis of T2DM and DN by evaluating its serum expression in T2DM and DN patients. Second, to assess the performance of serum micro-RNAs 16 and 24 as endogenous control in TaqMan assays of micro-RNA analysis by real time PCR in such disease. Quantification of the expression of micro-RNA 152-3p by qRT-PCR was performed using serum of 70 subjects enrolled in this study and grouped into 20 apparently healthy non-diabetic participants (control group), 15 patients with T2DM without nephropathy (DM group) and 35 diabetic patients with nephropathy (DN group). In diabetic patients with nephropathy (DN) (P<0.001), or without nephropathy (DM) (P 0.004), the expression of micro-RNA 152-3p demonstrated a significant elevation in comparison to the controls. Also, the level of micro-RNA 152-3p showed a positive correlation with HbA1c and the duration of diabetes mellitus. The severity of nephropathy as evaluated by markers of renal disease progression; estimated (e)GFR and albumin/creatinine ratio (ACR) revealed a significant correlation with the level of micro-RNA 152-3p. In the same context, serum level of micro-RNA 152-3p was elevated in diabetics with advanced stage of nephropathy (macroalbuminuria) versus the rest of diabetics (without albuminuria and with microalbuminuria). Two one sided T procedure provided a strong statistical support for equivalence of both micro-RNA s 16 and 24. In conclusion, such findings may indicate a pathologic role of micro-RNA 152-3p in Type 2 diabetes mellitus and in the progression of diabetic nephropathy.