Mesotherapy with various drugs is widely used in cosmetics, but the effect of the drugs on the skin should be scientifically grounded. Objective — the study was aimed at investigating the effect of mesotherapy with thymic and epiphyseal polypeptides, as well as the preparation containing nucleic acids on the immunohistochemical parameters of the skin. Material and methods. Three patients were administered with the nucleotide preparation, low molecular weight fractions of thymic and epiphyseal polypeptides, isotonic NaCl solution and underwent skin nidling on a limited area of the skin 1 week before elective surgery for abdominoplasty and scar excision using the “deep multipuncture” technique. In 1 week, expression of p53, Bcl-2, Ki-67, HLA-DR, and EGFR receptor-related markers was examined in cryostat sections of the bioptates using immunohistochemistry. Results. One week after mechanical needle trauma to the skin, no significant differences with the intact skin were detected in terms of the investigated markers. Injection of isotonic NaCl solution can facilitate proliferation of epidermal cells. The preparation containing nucleic acids inhibits epidermal and dermal cell proliferation but significantly increases the amount of antigen-presenting cells in the epidermis. Thymic polypeptides cause maximum increase in the amount of antigen presenting cells in the epidermis, while reducing their proliferative activity, and the most pronounced decrease in cell proliferation in the dermis, where they increase anti-apoptosis characteristics more than other drugs. Epiphyseal polypeptides increase the number of antigen-presenting and proliferating cells in the epidermis and, to a small extent, anti-apoptosis characteristics in the dermis. Conclusion. Immunohistochemical parameters of the skin vary depending on the manipulations and reflect the impact of the study drugs.