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Purpose: Diabetic retinopathy (DR) is still a leading cause of blindness. The role of miRNAs in diabetic retinopathy still needs more research. We aimed at validating the role of circulating miRNAs: 21,181C and 1179 in early detection, dynamic monitoring, and management of DR. Methods: Whole blood samples were collected from 180 diabetic patients and 60 normal individuals as control. The diabetic patients were subdivided into 60 subjects without retinopathy, 60 with non-proliferative diabetic retinopathy (NPDR), and 60 with proliferative diabetic retinopathy (PDR). Gene expression of miR-21, miR-181c, and miR-1179 were estimated in each sample using two-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Results: MicroRNA 181c and miRNA 1179 were significantly higher among PDR group compared to NPDR,W DM and control groups, while no significant difference was detected regarding miRNA 21. The areas under the receiver operating characteristic (ROC) curves of the validated two-serum miRNAs were 0.983 and 0.927 respectively. Combination of miRNA 1179 and miRNA 21 improved the accuracy rate to 90%. Combination of miR-181c and miR-1179 possessed high ability to discriminate between PDR and NPDR with an accuracy rate of 100%. Conclusion: MicroRNAs play a role in pathogenesis of diabetic retinopathy. In our study, miR-181c and miR-1179 were significantly high in PDR patients compared to NPDR and controls hence can be used to anticipate and follow up the progression. MicroRNA antagonists or mimics can be tried as new medications to modify DR by reducing the rate of progression, and subsequent blindness. [ABSTRACT FROM AUTHOR]