Wound healing is a complex biologic process evolving in three phases: inflammation, proliferation, and tissue remodeling controlled by numerous growth factors and cytokines. Oral mucosa wounds heal with significantly less important scars with less numerous macrophages and mast cells and more numerous myofibroblasts than cutaneous counterparts. We analyzed 32 cutaneous and 32 oral mucosa scars for TGFbeta1, TGFbeta2, TGFbeta3, TNFalpha, PDGF BB and FGF1 expression in mesenchymal cells, endothelial cells, macrophages, and multinucleated giant cells. We identified differences in the expression of profibrotic and antifibrotic factors in oral mucosa and skin scars; TGFbeta2 was positive in cutaneous multinucleated giant cells, TNFalpha was positive in cutaneous macrophages, and both were negative in oral mucosa while TGFbeta3 was positive in oral macrophages and mostly negative in cutaneous ones. PDGF BB and FGF1 were positive in oral endothelial cells and oral macrophages and negative in macrophages with opposite positivity pattern in cutaneous scars. Based on these findings, macrophage seems to be the key player in modulating pro- and antifibrotic processes in wound regeneration.