Background and Objective: Radiofrequency represents the most recent skin-rejuvenation treatment. The aim of this study was to study the changes in tissues and cells, as well as in the thickness and structure of the skin of guinea pigs following several sessions of radiofrequency. Materials and Methods: Six sessions (1 session/week) of radiofrequency (Thermafine Lift device, Grupo Solilá ser, S.L., Girona, Spain) were applied to the skin of guinea pigs. Biopsies were taken following each session and 2 months following the last application. The resultant samples were included in paraffin via the usual method, sectioned at 5 mm and stained with Haematoxylin-Eosin, Alcian blue, Toluidine blue, van Gieson's and Verhoeff's stains. These techniques were used in order to observe possible changes in the thickness and structures of the skin: mucopolysaccharides and collagen and elastic fibres. Results: The most relevant changes were found in the papillary dermis which underwent an expansion due to oedema and vascular congestion (first half of the experiment), followed by an increase in cellularity and the accumulation of intercellular substance. An increase in collagen, elastic fibres and mucopolysaccharides was observed. Conclusion: The Thermafine Lift device caused no significant macroscopic or microscopic alterations in the skin of guinea pigs, yet increased both the thickness, as well as the mucopolysaccharide, collagen and elastic-fibre content.