Stromal-epithelial interactions are important during wound healing. Transforming growth factor-␤ (TGF-␤) signaling at the wound site has been implicated in re-epithelization , inflammatory infiltration, wound contraction , and extracellular matrix deposition and remodeling. Ultimately , TGF-␤ is central to dermal scarring. Because scarless embryonic wounds are associated with the lack of dermal TGF-␤ signaling , we studied the role of TGF-␤ signaling specifically in dermal fibroblasts through the development of a novel , inducible , conditional , and fibroblastic TGF-␤ type II receptor knockout (Tgfbr2 dermalKO ) mouse model. Full thickness excisional wounds were studied in control and Tgfbr2 dermalKO back skin. The Tgfbr2 dermalKO wounds had accelerated re-epithelization and closure compared with controls , resurfacing within 4 days of healing. The loss of TGF-␤ signaling in the dermis resulted in reduced collagen deposition and remodeling associated with a reduced extent of wound contraction and elevated macrophage infiltration. Tgfbr2 dermalKO and control skin had similar numbers of myofibroblastic cells , suggesting that myofibroblastic differentiation was not responsible for reduced wound contraction. However , several mediators of cell-matrix interaction were reduced in the Tgfbr2 dermalKO fibroblasts , including ␣1 , ␣2 , and ␤1 integrins , and collagen gel contraction was diminished. There were associated deficiencies in actin cytoskeletal organization of vasodilatorstimulated phosphoprotein-containing lamellipodia. This study indicated that paracrine and autocrine TGF-␤ dermal signaling mechanisms mediate macrophage recruitment , re-epithelization , and wound contraction. (Am J Pathol 2010, 176:98 -107;