We show here that the α, β, and γ isotypes of peroxisome proliferator–activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfollicular epithelium after birth. Interestingly, PPARα and β expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing. Using PPARα, β, and γ mutant mice, we demonstrate that PPARα and β are important for the rapid epithelialization of a skin wound and that each of them plays a specific role in this process. PPARα is mainly involved in the early inflammation phase of the healing, whereas PPARβ is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPARβ mutant primary keratinocytes show impaired adhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPARα and β in adult mouse epidermal repair.