To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated thein vivoeffects of transforming growth factor-β by injection into subcutaneous tissue of newborn mice. Histological examination revealed that TGF-β1, β2, and β3 induced granulation tissue formation after 3 days of injection, while these changes had disappeared after 7 days. The changes after 3 days of injection were more pronounced in the tissue injected with TGF-β2 or β3 than that with TGF-β1.In situhybridization analysis indicated that connective tissue growth factor mRNA was strongly expressed in the fibroblasts at the site of TGF-β injection, which suggested that fibroblasts were activated by TGF-β. Next, we investigated the cooperative effects of TGF-β and other growth factors including basic fibroblast growth factor (bFGF). The simultaneous application of TGF-β and bFGF caused apparent tissue fibrosis which persisted for at least 2 weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection. Thus, we succeeded in establishing an animal model of skin fibrotic disorders by the exogenous addition of growth factors, and this animal model will be useful for future studies in this area.