Wound healing proceeds by the concerted action of a variety of signals that have been well identified. However, the mechanisms integrating them and coordinating their effects are poorly known. Herein, we reveal how PPARβ/δ (PPAR: peroxisome proliferator‐activated receptor) follows a balanced pattern of expression controlled by a crosstalk between inflammatory cytokines and TGF‐β1. Whereas conditions that mimic the initial inflammatory events stimulate PPARβ/δ expression, TGF‐β1/Smad3 suppresses this inflammation‐induced PPARβ/δ transcription, as seen in the late re‐epithelialization/remodeling events. This TGF‐β1/Smad3 action involves an inhibitory effect on AP‐1 activity and DNA binding that results in an inhibition of the AP‐1‐driven induction of the PPARβ/δ promoter. As expected from these observations, wound biopsies from Smad3‐null mice showed sustained PPARβ expression as compared to those of their wild‐type littermates. Together, these findings suggest a mechanism for setting the necessary balance between inflammatory signals, which trigger PPARβ/δ expression, and TGF‐β1/Smad3 that governs the timely decrease of this expression as wound healing proceeds to completion.