The aim of research was to study participation of skin mast cells of C57BL/6J mice in the mechanisms of fibrillogenesis under zero gravity conditions.Material and methods. A histochemical study of the skin from the lateral thigh of the C57BL/6J mice exposed aboard the International Space Station for 21–24 days, as well as animals of the control groups – vivarium, baseline and ground, – was performed. Mast cells were detected with an assessment of the secretome participation in collagen fibrillogenesis after protocols of separate and combined histochemical staining with Giemsa’s solution and silver impregnation. Microsections were analyzed using a hardware-software complex based on a ZEISS Axio Imager. A2 research microscope (Carl Zeiss, Germany).Results. Zero-gravity conditions led to a change in the activity of mast cells degranulation and histotopographic localization, a decrease in the content of large granules, a decrease in the cooperation with fibroblast/ fibrocyte and the intensity of fibrillogenesis, a decrease in co-localization with the reticular fibers of the extracellular matrix of the skin tissue, as well as a modification of the intrapopulation interaction. The article discusses possible molecular-cellular causes of changes in the activity of fibrillogenesis and polymerization of tropocollagen molecules into supramolecular fibrous structures in the skin connective tissue aboard the International Space Station.Conclusion. Zero gravity conditions caused an increase in the secretory activity of mast cells in the skin, simulated the processes of intercellular signaling with other representatives of the specific tissue microenvironment, and resulted in the weakening of collagen fibrillogenesis.