PURPOSE: The aim of this study is to convert tretinoin (Tr), an active pharmaceutical ingredient (API), into ionic liquid for improving aqueous solubility and permeability of Tr in transdermal drug delivery applications. METHODS: Three ionic liquids of Tr (TrILs) were synthesized through neutralization reactions, which were characterized to confirm the compositions and ionic interactions. The in vitro drug release studies and skin penetration tests were carried out to assess the performance of formulations containing TrILs. RESULTS: The TrIL formed by choline and Tr at the molar ratio of 2:1 (2[Ch][Tr]), was found to have prominent solubility, stability as well as permeability. In contrast with the insoluble Tr, 2[Ch][Tr] presented as clear and transparent aqueous solution even after diluted to 14%. The aqueous solution of 2[Ch][Tr] demonstrated better permeation effect, of which the solution with 20% of 2[Ch][Tr] showed the optimal delivery efficiency in both epidermis (2.09 ± 0.18‰) and dermis (3.31 ± 0.48‰), realizing the improvement on the permeability of API. Meanwhile, TrILs can be easily fabricated as o/w emulsions as transdermal formulation. The emulsions are also able to improve the skin permeability of Tr, though the enhanced effect is inferior to TrILs solutions. CONCLUSIONS: Ionic liquid technology can be used to improve solubility and permeability of Tr, providing a high potential strategy for the development of topical formulations and the desired transdermal application of drugs.