Background: Diabetic Retinopathy (DR), a leading cause of acquired visual loss, is a microvascular complication of DM, among the middle-aged and economically active population. At present, there is a lack of accuracy and specificity in our ability to identify this particular cohort. As the disease remains asymptomatic until the pathology is significantly advanced, screening to detect it during the early stages is necessary. Ability of miRNAs to alter or fine tune the expression of key regulators in various physiological processes and pathophysiological disease states makes them novel targets for diseases such as diabetic complications. Aim: The present work aimed to find out the possibility to use the expression pattern of miRNAs (146a, 21, and 34a) as biomarkers for early detection of DR in addition to the underling mechanisms. Also, to evaluate the correlation between them in each stage of DR to help in diagnosis by simple noninvasive methods.  Patients and methods: Eighty patients with type 2 diabetes mellitus were involved in this study and diagnosed after investigation into normal, mild, moderate, severe NPDR and PDR patients. miRNAs 1436a,-21 and 34a were evaluated in the serum of patients in each group. Results: The present study revealed that the levels of miRNA-146 and miRNA -21 are increased in serum of DR patients in direct relation with the severity. However, serum miRNA-34a is decreased with progression of the disease. Conclusion miRNAs level in the serum of diabetic patients can be used as diagnostic biomarkers of DR.