Diabetic retinopathy (DR) is a microvascular complication that develops in diabetic individuals. There are currently no methods to detect the onset or progression of DR. Biomarkers can help identify the subset of diabetics who are at high risk of developing DR or those DR patients with a high probability to progress quickly to advanced stage. In this study, we examined the serum microparticles as a source of biomarkers for DR. We profiled the microparticle proteome and compared across six different sample groups representing the onset and progression of DR. We found that the microparticle proteins participate in DR pathogenesis. We also validated eight of these proteins and found two to be biomarkers for DR.