Background: Diabetic retinopathy (DR) is a major cause of blindness in working-age individuals in the developed countries. Studies have found that diabetic macular edema (DME) is a major cause of visual impairment in patients with diabetes mellitus (DM). Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of DME. Material and Methods: Eighty-two patients (153 eyes) with DME were divided into two treatment groups. Group 1 (37 patients, 68 eyes) was treated with injections of the anti-VEGF agent brolucizumab according to the one plus pro re nata (PRN) regimen (once plus as needed) only, whereas group 2 (45 patients, 85 eyes) received a combination of “one plus PRN” brolucizumab therapy with subthreshold micropulse laser exposure (SMPLE). Before and after treatment, a comprehensive ophthalmological examination was performed, including the best-corrected visual acuity (BCVA) and the height of retinal edema in the central fovea as assessed by optical coherence tomography. The parameters were assessed at 1, 3, 6 and 12 months after treatment. Results: The percentage of patients with no need for additional anti-VEGF injections was substantially higher in the combined therapy group than in the monotherapy group (68.5% versus 12%, respectively, p <0.001). Conclusion: The combination treatment (intravitreal brolucizumab combined with SMPLE) for DME was effective in 68.5% of cases within 12 months. In this way, a steady resorption of DME is accomplished through antivasoproliferative and prolonged effects of brolucizumab and the SMPLE session.