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In fibrotic reactions, excessive deposition of ECM by the activated fibroblasts determines scar formation and functional failure. Although these events critically depend on the activity of a plethora of growth factors and cytokines, TGF\u03b21 is a unique player controlling the immune response and proliferation of many cell types. Different cell types contribute to its release and activation, which is also regulated by the interaction with the ECM and by mechanical forces. The aim of this study was to elaborate whether fibroblast\u2010derived TGF\u03b21 plays a critical role during these processes. The data demonstrate a dynamic expression of TGF\u03b21 during tissue repair. Cell\u2010specific ablation of <jats:italic>Tgfb1<\/jats:italic> in fibroblasts revealed that deletion of TGF\u03b21 attenuates bleomycin\u2010induced skin fibrosis and perturbs maturation of granulation tissue in skin wounds. Absence of fibroblast\u2010derived TGF\u03b21 induced vascular alterations (less vascular density and branching, haemorrhage) in early wound healing. This was associated with alterations in the formation of stable ECM structure. This can be explained by paracrine regulation of endothelial cells or pericytes by fibroblast\u2010released TGF\u03b21 and by impaired expression of pro\u2010angiogenic factors in TGF\u03b21\u2010deficient fibroblasts. 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