PURPOSE: This study investigated retinal blood flow alterations in diabetic macular edema (DME) using ultra-widefield optical coherence tomography angiography (OCTA). METHODS: We enrolled 31 healthy controls (NC, 56 eyes), 40 diabetes patients without diabetic retinopathy (DM, 79 eyes), 25 non-proliferative diabetic retinopathy patients (NPDR, 47 eyes), and 42 DME patients (DME, 54 eyes). OCTA images were analyzed using five-quadrant and concentric zonal divisions to assess vascular density (VD) in the superficial (SVC) and deep vascular complexes (DVC). RESULTS: In the DM group, nasal SVC VD was significantly reduced in the N11, N16, and N21 regions. NPDR patients showed widespread SVC VD reduction compared to controls and DM patients, while DME patients exhibited elevated SVC VD in the peripheral retina (11-21 mm). DVC changes were significant only in the macular area in NPDR group, with DME patients showing increased VD in all regions except I21. Peripheral DVC VD (T11, T16, S16) strongly correlated with DME on ROC analysis. CONCLUSIONS: Nasal SVC vascular alterations are among the detectable early intergroup differences in preclinical DR, and peripheral DVC VD is closely correlated with the presence of DME.