Background: To evaluate macular microcirculation in patients with unilateral diffuse diabetic macular edema (DME) in order to determine whether the alteration in macular microcirculation is associated with development of diffuse DME without vitreomacular traction. Methods: According to the presence of epiretinal membrane (ERM), 27 patients having unilateral diffuse DME were divided into DME without ERM (non-ERM-DME group, n = 12) and with ERM (ERM-DME group, n = 15). Twelve patients with macular edema associated with unilateral branch vein obstruction (BVO) and 10 nondiabetic healthy subjects were enrolled as controls. Macular blood flow measured by Heidelberg retinal flowmeter was compared between the edematous eye and the nonedematous fellow eye of each patient and between groups. The macular thickness was evaluated with optical coherence tomography. Results: The mean macular blood flow was significantly higher than that of the contralateral eyes in edematous eyes of non-ERM-DME group (798.8 vs. 379.8 AU, p < 0.001). By contrast, in the ERM-DME group, the mean macular blood flow of DME eyes was similar to that of fellow eyes (575.9 vs. 596.4 AU, p = 0.538). The macular capillary blood flow in patients with BVO was not significantly different compared with nondiabetic controls (p = 0.967). Conclusions: The results suggest that the alteration of macular microcirculation may play a role in the pathogenesis of diffuse DME without vitreomacular traction.