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OBJECTIVE To study the effect of solvents on the permeation of leflunomide in excised mouse skin. METHODS Modified Franz-diffusion cell adopted as apparatus for in vitro skin permeation, excised mouse skin as permeation barrier and permeability as index, the concentration of leflunomide in the samples was measured by HPLC. RESULTS Ethanol has enhancement effect on the permeability of leflunomide, propylene glycol and lower concentration DMI have little effect on the permeability of leflunomide. CONCLUSIONS These solvents can be used in the skin local preparations of leflunomide.