Finally, topical TF is highly effective in reducing swelling, fibrosis and inflammation and the overall pathology of lymphedema.<h4>Conclusions</h4>Our findings suggest that lymphedema is a chronic inflammatory skin disease, and topically targeting keratinocyte inhibition may be a clinically effective therapy for this condition.<h4>Key points</h4>Activated keratinocytes play a key role in the pathophysiology of secondary lymphedema through PAR2 by producing Th2-inducing cytokines that modulate skin inflammatory responses. Here, TF is linked to lymphedema.