Finally, we show that a topical formulation of pirfenidone (PFD), a small‐molecule inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis, significantly decreased TGF‐β1 signaling, reduced fibrosis and decreased lymphedema formation in a mouse model. This evidence concerns the gene TGFB1 and lymphedema.