Introduction A collagen/gelatin sponge (CGS) is a new scaffold that promotes wound healing by slowly releasing fibroblast growth factor (FGF)-2. FGF-2 induces mitogenesis, angiogenesis, and adipogenesis. In this study, the adipogenesis-inducing effects of CGS combined with FGF-2 in the subcutis of mice were evaluated. Methods Collagens/gelatin sponges (10 x 5 mm) were impregnated with 50 mu L of FGF-2 solution (10 or 100 mu g/mL). A CGS (Gunze Corp, Osaka, Japan) combined with FGF-2 was implanted subcutaneously into the thoracic region of mice. At 1, 2, 3, and 4 weeks, samples were collected for hematoxylin and eosin staining, von Willebrand factor immunostaining, and perilipin immunostaining to examine adipose tissue localization and angiogenesis. A CGS with only saline solution was prepared as a control. Results Adipocytes in the collagen fibers appeared at 3 weeks, and a zonal fat layer was noted under the panniculus carnosus at 4 weeks in the FGF-2-combined CGS groups. The fat layer was significantly thicker in the FGF-2 (100 mu g/mL) group than in the FGF-2 (10 mu g/mL) group. In the control group, no fat pad was newly formed. The number of newly formed vessels in the FGF (10 mu g/mL) and (100 mu g/mL) groups was significantly greater in the FGF-2 group than in the control group. Conclusion This study presents a promising method to enhance adipogenic effects in the murine subcutis using CGS combined with FGF-2, representing a potential technique for soft tissue reconstruction.