Background: Various kinds of biomaterials are being used for soft tissue augmentation in plastic surgery. Organic molecules are usually absorbed in a short amount of time. Inorganic molecules stay in the body for a longer period of time, but are prone to cause various reactions; therefore, none of them are ideal filler substances. Objective: This study was designed to examine the clinical and histologic effects of injection of cultured fibroblasts in hyaluronic acid as a filler material. The advantages, disadvantages, and side effects of the procedure were examined during the study. Methods: Skin biopsies obtained from the backs of 30 Sprague Dawley rats were used in the study. Dermal fibroblasts obtained from these biopsies were cultured for 21 days and, after 3 weeks, autologous labeled cultured fibroblasts of the rats were injected intracutaneously alone and mixed with hyaluronic acid. Injections of culture medium and hyaluronic acid were also performed as control groups. At the end of the fourth and eighth months, skin biopsies were taken from the injection sites and normal skin and examined under light and electron microscopes. Results: The injected fibroblasts, elastin, and collagen production were analyzed and found to be stable, long-lasting, and well tolerated. No complications were observed. Conclusions: Cultured human dermal fibroblasts combined with hyaluronic acid can provide a suitable, biocompatible, and long-lasting material and should be regarded as a new method in dermal renovation even beyond their temporary filling effect.