Introduction. As there is insufficient evidence to date to determine phlebotropic drug preferences, further research in this area is warranted. Aim. To evaluate the effect of topical and oral phlebotropic agents on vascular wall permeability in preclinical studies. Materials and methods. The objects of the study were 6 phlebotropic agents for external and oral use, which were administered according to the recommendations specified in the instructions for use, 2 hours before the trypan blue. The model for preclinical studies: the xylene petechiae test with trypan blue staining. The evaluation criterion was the intensity of staining, which was expressed semiquantitatively (points). The test system was 100 white male outbred conventional mice. Results and discussion. Heparin + EPL + escin (Detragel) significantly reduces the intensity of staining in the xylene petechiae test. It was found that with a single external application reduces the intensity of staining by 25.0% compared to the control, which significantly by 60.0% exceeded the effectiveness of the drug heparin 1000 IU; with a course application of 15 days in 2 times, which significantly, least by 50%, exceeded the effect of the drug heparin 1000 IU and cosmetic product containing troxerutin. MPFF 1000 mg (Detralex) at a single oral administration significantly reduced the intensity of staining by 35.0% compared to the control group, which significantly by 69.2% exceeded the effectiveness of the reproduced preparations of MPFF and diosmin 600 mg. The indicated results are explained by differences in production technology, composition of components and are consistent with the known data on clinical efficacy of different groups of venotonics. Conclusion. In preclinical studies on the model of xylene petechiae with trypan blue staining, high efficacy of the original drug MPFF 1 (Detralex) at a single oral application and the drug heparin + EPL + escin (Detragel) at external single and course application for 15 days was established, which showed a significant difference with the control group, not less than 50% exceeded the efficacy of analogues and may indicate the effect on the permeability of the vascular wall.