Abstract Purpose To examine changes in retinal and choroidal vasculature in diabetes mellitus across the range of diabetic retinopathy (DR) severities using optical coherence tomography angiography (OCTA) and compare the patterns of vascular changes. Methods We conducted a cross-sectional study enrolling 296 patients (498 eyes) with diabetes mellitus. Swept-Source OCT Angiography variables in both retina and choroid, including perfusion density (PD), vessel density (VD), large vessel density (LVD) in both superficial and deep layer of retina and CC flow voids (FD) density of the choroid were quantified. Correlations between OCTA parameters and DR severity, visual acuity and studied factors were performed. Results Totally 498 eyes including 176 had no DR, 160 had mild NPDR, 98 had moderate NPDR, 11 had severe NPDR, 41 had PDR with PRP, and 12 had PDR without PRP. Choriocapillaris (CC) flow voids density increased with increasing DR severity (17.06% vs 17.41% vs 17.60% vs 17.62% vs 18.05% vs 18.41%, p-trend = 0.0004), FAZ area increased with DR severity in both superficial and deep layer (superficial layer p trend=0.0027; deep layer p trend=0.0022). Visual acuity correlated negatively with CC flow voids (Pearson’s ρ = 0.09, p = 0.04) and superficial FAZ area (Pearson’s ρ = 0.22, p < 0.001), while inversely correlated with SCP PD (Pearson’s ρ = −0.15, p < 0.001) and VD (Pearson’s ρ = −0.15, p < 0.001), as well as DCP PD (Pearson’s ρ = −0.21, p < 0.001) and VD (Pearson’s ρ = −0.19, p < 0.001). Conclusion Choriocapillaris ischemia increased, FAZ area enlarged, and total retina perfusion density decreased with increasing DR severity. The deep layer and large vessels may change in early stage before DR progresses to PDR. More ischemia and vessel tortuosity are correlated with worse visual acuity and higher HbA1c level. OCTA can be utilized to detect both large and small vascular changes in both the retina and choroid in DR patients.