Mesenchymal stem cells (MSCs) have unique properties that ensure the regeneration of damaged tissues, which allows using them in the cell therapy of various diseases. The realization of these properties is mainly related to the interaction of MSCs with macrophages. Aim. To study the interaction of the human umbilical cord MSCs with macrophages in vivo using a model of sterile inflammation of the peritoneal cavity in mice. Methods. Cytological methods for assessing acute inflammation of the peritoneal cavity of mice, isolation and cultivation of the human umbilical cord MSCs, study of the expression of the MSC surface markers by flow cytometry, determination of the phagocytic activity of mononuclear cells of peritoneal cavity, isolation of mononuclear RNA, RT-PCR, methods of statistical analysis. Results. The dynamics of the development of the MSCs’ therapeutic effect after their transplantation into the peritoneal cavity of mice was studied; a method for assessing the therapeutic activity of various MSC preparations was developed; the fast polarization of macrophages to the M2 state after the injection of MSCs was shown, by studying the phagocytic activity of macrophages and expression of the IL-10 gene. Conclusions. The most effective method to increase the therapeutic potential of MSCs is preconditioning with low doses of H₂O₂.