The current strategy for the treatment of venous trophic ulcers (VTU) suggests differentiated approach and a combination of conservative and surgical methods. This paper presents the results of the study of efficacy of systemic enzyme therapy (Phlogenzym by Mucos Pharma, Germany) in patients with varicose veins of lower extremities (CEAP class C6) and stage I, II and III VTU. The study included 38 patients aged 12 to 82 years. The patients were divided into the experimental (n = 20) and the control (n = 18) groups. The treatment lasted 1 month. Silcofix Professional wound dressings (Pharmaplast, Egypt) were used. All patients received Detralex (Les Laboratoires Servier, France) and wore class 2 and 3 knee-high compression socks. Patients of the experimental group also received Phlogenzym for 30 days (3 tablets 3 times a day). Total ulcer epithelization was observed in 8 (40 %) patients by week 3, and in 18 (90 %) patients by the end of treatment compared to 4 (22 %) and 9 (50 %) patients in the control group, respectively. In the control group, the regenerative process in the area of the ulcerous defect was less prominent compared to the experimental group. Immunoassays revealed a significant reduction in CD4⁺CD25^Bright cells and increased levels of CD4⁺CD45RO⁺ T-lymphocytes in the experimental group, corresponding with the observed positive clinical response. The use of immunomodulatory drug Phlogenzym contributed to a more rapid regression of clinical symptoms of chronic venous insufficiency and faster healing of stage I–III venous trophic ulcers.