Quantitative imaging using optical coherence tomography angiography (OCTA) could provide objective tools for the detection and characterization of diabetic retinopathy (DR). In this study, we developed a novel quantitative approach using OCTA images to delineate the vessel orientation pattern of a specific region of interest, which is an orientation distribution curve depicting the probability of vessels at each angle from 0 to 360 degrees. Three quantitative metrics including vessel preferred orientation, vessel anisotropy and vessel mass were extracted from the orientation pattern and analyzed in each of eight 45° sectors at the macula. Differential retinal microvascular orientation patterns were observed between three healthy subjects and three subjects with DR. Greater variability of vessel preferred orientation (p<0.001) and vessel mass (p<0.001) was exhibited among subjects with DR than healthy in eight sectors. In the nasal-superior sector, there was a significant difference between healthy and DR subjects in preferred orientation and vessel anisotropy. The vessel mass characterized from the vascular orientation pattern was shown to be strongly correlated with the traditionally reported vessel density (p<0.00001). These preliminary results suggest the feasibility and advantage of our vessel orientation-based quantitative approach using OCTA to characterize DR-associated changes in retinal microvasculature.