The issues of skin regeneration during thermal injury are an ur-gent problem of modern biomedicine. The quality and speed of res-toration of the damaged epidermis largely ensures the quality of life of patients. The optimal method of wound treatment depends, inter alia, on knowledge of the structural and functional features of the extracellular matrix of the connective tissue of the dermis, including the amphora and fibrous components. Material and methods. In a study on adult Wistar rats, we modeled second degree burns of the posterior surface of the torso with an area of 10% of the body surface for the purpose of histological and immunohistochemical assessment of the involvement of mast cells in the wound process and their importance in the implementation of collagen fibrillogenesis in various protocols for the treatment of burn wounds. A planimetric analysis was carried out to obtain quantitative data on the content of mast cells per mm2 of the skin, their histotopography and morphofunctional typing were determined to assess the secretory activity. Results. The study revealed that the burn wound caused an increase in the population of skin mast cells with certain histotopo-graphic patterns, in particular, predominant accumulation in the peripheral region of the alteration zone. An increase in the secre-tory activity of mast cells led to a systemic reconstruction of the extracellular matrix, stimulating the healing processes by activat-ing the formation of the fibrous component of the connective tissue. After thermal exposure, a significant increase in tryptase expression in the mast cell population was revealed when using water with an increased content of molecular hydrogen. Conclusion. The revealed features of various protocols of wound management in the efficiency of regenerative processes are due to the degree of involvement of mast cells in fibrillogenesis using direct and indirect pathways. Thus, the molecular mechanisms of extracellular matrix remodeling, induced by the secretory activity of mast cells, are promising targets for intensifying the regenerative effects of pharmacological agents. © 2021, Human Stem Cell Institute. All rights reserved.