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Persistent inflammation and impaired repair in dermal wound healing are frequently associated with cell–cell and cell–matrix miscommunication. A direct coculture model of primary human myofibroblasts (MyoFB) and M‐CSF‐differentiated macrophages (M‐Mɸ) in fibrillar three‐dimensional Collagen I (Coll I) matrices is developed to study intercellular interactions. The coculture experiments reveal the number of M‐Mɸ regulated MyoFB dedifferentiation in a dose‐dependent manner. The amount of MyoFB decreases in dependence of the number of cocultured M‐Mɸ, even in the presence of MyoFB‐inducing transforming growth factor β1 (TGF‐β1). Gene expression analysis of matrix proteins (collagen I, collagen III, ED‐A‐fibronectin) confirms the results of an altered MyoFB phenotype. Additionally, M‐Mɸ is shown to be the main source of secreted cytokine interleukin‐10 (IL‐10), which is suggested to affect MyoFB dedifferentiation. These findings indicate a paracrine impact of IL‐10 secretion by M‐Mɸ on the MyoFB differentiation status counteracting the TGF‐β1‐driven MyoFB activation. Hence, the in vitro coculture model simulates physiological situations during wound resolution and underlines the importance of paracrine IL‐10 signals by M‐Mɸ. In sum, the 3D Coll I‐based matrices with a MyoFB–M‐Mɸ coculture form a highly relevant biomimetic model of late stages of wound healing. [ABSTRACT FROM AUTHOR]