This work was aimed at studying the effect of intradermal injection of hyaluronic acid (HA) modified with biologically active substances on morphofunctional state of skin. The effect of subcutaneous and intradermal injection of modified HA on the morphological structure and ultrastructure of skin was studied in 180 rats and three minipigs. The clinical evaluation of the efficacy and tolerability of the modified HA was performed; the morpho-functional parameters of involutional skin changes during the intradermal injection of modified HA were examined in 90 patients. Histological and electron microscopy methods were used during the experiment. The skin condition of the patients was assessed using results of non-invasive diagnostics of skin functions and morphology (corneometry, sebumetry, elastometry, ultrasonic dermal scanning, visual scanning, and confocal laser scanning microscopy). Histological examination revealed an increase in skin regeneration at the site of gel injection and high biocompatibility of the injection with tissues. The clinical trial results demonstrated good tolerability and clinical efficacy of modified HA.