Purpose — to evaluate clinical effectiveness of aflibercept therapy for patients with diabetic macular edema (DME) — both naïve to the drug and unresponsive to previous anti-VEGF treatment. Material and methods. The study included 127 patients (127 eyes) divided into two groups. The first group consisted of 100 primary DME patients (100 eyes) with mean age of 68.48±2.56 years and average disease duration of 12.50±7.85 years. The second group comprised 27 patients (27 eyes) with resistant macular edema who had received three or more 0.5 mg ranibizumab loading injections. Their average age was 66±4.12 and the mean number of previous anti-VEGF injections before changing therapy was 4.56±1.21. The evaluation parameters included Best Corrected Visual Acuity (BCVA) and Central Retinal Thickness (CRT) that were assessed initially and after each 2 mg aflibercept injection (at 1-month intervals during the 6 months of DME therapy). Results. The average number of aflibercept injections in the first group was 4.34±1.22. BCVA improved in 100% of patients of that group after the 3rd injection with resulting mean value of 0.32±0.15. Maximum BCVA improvement was seen after the 6th injection amounting to 0.46±0.2. CRT decreased in 100% of patients of that group after the 1st injection. One month after the therapy start, CRT decreased in average by 17.96% — to 370.89±50.55 µm; at 3 months, CRT was 344.65±48.56 µm; after 6 month — 283.40±49.76 µm. All patients of the second group had retinal morphology restored, visual function improved in 55% of patients. Mean CRT decrease was 180±44 µm, BCVA improvement — 0.13±0.08, mean number of aflibercept injections — 4.86±0.9. Conclusion. Aflibercept can be used as first-choice drug for treatment of DME patients (both therapy-naïve and unresponsive to previous ranibizumab therapy) to improve anatomical parameters and visual function.