Taking into account the pathogenesis peculiarities of appendicular pylephlebitis, the risk group includes patients with a retrocecal location of the appendix, gangrenous and perforating appendicitis, the course of which was complicated by peritonitis or abscess. The purpose of our clinical-experimental study was to justify the method of pathogenetic treatment of acute appendicular pylephlebitis based on an experimental model of portal hypertension. Acute experiments were performed on male Wistar rats and outbred dogs. Clinical studies were prospectively-retrospective. In addition to traditional methods of treatment, we used the developed technique of draining the retroperitoneal space and introducing antibacterial compositions in a complex with a 10% dimethylsulfoxide (DMSO) solution was used. On the basis of experimental data, it was established that a 10% solution of DMSO complexed with a dye, when injected transperitoneally in the ileocecal angle area, preferentially penetrates the lymphatic and portal systems, even in conditions of portal hypertension. This is explained by the peculiarities of the anatomical structure. The use of the method of intraperitoneal administration of antibiotics in combination with DMSO is pathogenetically justified in patients with appendicular pylephlebitis, as it achieves local sanitation of the immediate source and primary ways of spreading the infection. Implementation of the developed method of prevention and treatment of acute pylephlebitis of appendicular genesis as part of improved treatment tactics allows to improve treatment results by likely reducing the frequency of postoperative complications from 18.7% to 2.7% (χ2 = 20.02, 95% CI 9.25-23.8) and the duration of hospitalization from 22.8 days to 8.5 days.