BACKGROUND: Various techniques have been employed in aesthetic medicine to combat skin aging, in particular that of the facial region. Hyaluronic acid is utilized to enhance moisture levels and extracellular matrix molecules. This study aims to histologically assess the effects of low molecular weight hyaluronic acid fragments combined with amino acids (HAAM) on facial skin rejuvenation through intradermal microinjections. METHODS: A total of twenty women, with an average age of 45 and ranging from 35 to 64 years old, participated in the study, including 8 in menopause and 12 in the childbearing age group. Mesotherapy was used to administer HAAM to the patients. Prior to and three months after the treatment, each patient underwent small circular punch biopsies. Ultrasound examinations were conducted using B-mode, capturing 2D images in longitudinal or transverse orientations with frequencies ranging from 5 to 13 Mega-hertz (MY LAB X8, ESAOTE, Genova, Italy). A total of 60 ultrasound examinations were taken, with 30 collected before treatment and 30 after treatment. RESULTS: The histological analysis demonstrates an increase in fibroblast activity resulting in the production of Type III reticular collagen, as well as an increased number of blood vessels and epidermal thickness. However, the analysis of ultrasound data before and after treatment showed no statistical difference in skin thickness in malar area, chin and mandibular angle. CONCLUSIONS: Histological assessments indicate that subcutaneous infiltration of HAAM has a substantial impact on the dermis of facial skin.