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Background: The effects of low-intensity laser radiation (LILR) on the skin depend on the wavelength and density of the irradiation flux. Moreover, the vast receptor field of the skin facilitates the systemic influence of irradiation on the body., Aims: The objective of the present study was to evaluate the effects of low-intensity laser irradiation (LIRI) of the infrared range with a wavelength of 1270 nm on the skin of mice Balb/cNude., Material and Methods: The study was carried out with the use of the linear immunodeficient mice Balb/c nude obtained from the animal house of the Pushchino branch of the Academicians M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Biorganic Chemistry. The animals were irradiated once with a fiber laser of stimulated Raman scattering with a wavelength (λ) of 1270 nm, a power of 1.96 mW during the 2 min exposure at an intensity of 10 mW/cm 2 , and an energy flux density of 1.2 J/cm 2 . The histological studies and morphometry of the skin autoptate were performed. In adition, the expression of microRNA-21, -31, -130a, -191, -200c, -205, -218 was determined in the skin. Reverse transcription and real-time PCR reactions with Taq-Man probes and primers were performed on the nucleic acid amplifier CFX96 ('BioRad', USA).MicroRNA-191 was chosen as the reference gene. The bioinformation analysis of signaling pathways involving the studied microRNAs was performed using the DJANA miRPath database v.3.0., Results: A significant increase in the amount of keratinocytes of the basal layer was documented together with diffuse lymphoid-leukocyte infiltration of the interlobular connective tissue of the subcutaneous fat and endomysium after LILR. The pattern of microRNA expression was tissue-specific. An increase in the expression of micro-RNA-31 and-21 in the skin and a multidirectional change in miRNA-200 and -218 levels were shown. The bioinformation analysis showed that miR21 and miR31 were involved in the regulation of such signaling pathways as PI3K-Akt, Jak-STAT, MAPK, and mTOR of importance for carcinogenesis. Also, they have a signaling significance in the development of melanoma, kidney cancer, prostate cancer and malignant glioma., Conclusion: The data obtained in this study suggest activation of the tumor cell-specific and basic processes in the skin of immunodeficient Balb/cNude mice under the influence of low-intensity laser radiation with a wavelength of 1270 nm applied at a dose of 1.2 J/m 2 .