Background: Diabetes mellitus (DM) is a chronic disease characterized by insulin deficiency or its peripheral resistance resulting in hyperglycemia and non-enzymatic glycation of protein.The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels. MicroRNAs (miRNAs) are a class of highly conserved 19–25 nucleotide noncoding RNAs that regulate gene expression. Objective:This study aimed to assess plasma miR-27b expression in diabetic retinopathy patients as an early diagnostic parameter in both proliferative and non-proliferative and to assess the correlation between plasma levels of miR-27b with the clinico-pathological parameters of diabetic patients as well as determination of the level of thrombospondin-1 (TSP1). Patients and Methods: This study was conducted on 60 diabetic retinopathy Egyptian patients that were recruited from the Research Institute of Ophthalmology - RIO (Medical Retina Clinics) during their routine screening for diabetic retinopathy. Results: Micro RNA 27b shows a highly significant difference (increase) among PDR compared to non-PDR & control groups (P value: 0.001) and shows a moderately significant increase in expression in PDR group compared to control group (P value: 0.01). This significant increase in microRNA between PDR group and control group has the ability of being a non-invasive biomarker for diagnosis of PDR versus control group, as miRNA-27b expression showed AUC = 0.889 with (95% CI 0.744–1.000). The best cut-off point of miRNA-27b is 1.95 with 88.9% sensitivity & 100% specificity and the p value <0.001(highly significant). Conclusion: TSP-1 can act as a predictor for transformation of non-retinopathy stage to PDR stage. miRNA-27b has the ability to differentiate between the PDR and control group and could be considered a non invasive biomarker.