Cutaneous air-breathing is one of the air-breathing patterns in bimodal respiration fishes, while little is known about its underlying formation mechanisms. Here we examined the skin regeneration of loach (Misgurnus anguillicaudatus, a cutaneous air-breathing fish) and yellow catfish (Pelteobagrus fulvidraco, a water-breathing fish). The regenerated skins when their highest vascularization occurred and original skins of the two fishes were collected for RNA-seq and comparative analysis, aiming to investigate the molecular mechanism of cutaneous air-breathing formation in the loach.