There are two methods to treating onychomycosis. They are oral therapy and topical therapy. In this study we investigated the topical therapy. Penetration enhancer is necessary for effective topical dose of nail. KOH, NaOH and NaBH4 that have a potentiality as a penetration enhancer were dissolved in distilled water at 3% w/v concentration. And then nails are treated with penetration enhancers. The nail swelling rate(%) is calculated by using the nail weight of before and after experiment. The nails treated with penetration enhancer are fully dried and then we observed the surface of nails by using SEM and AFM. The three potential penetration enhancers showed high nail swelling rate and the surface of nails was more lifted than non-treating group or control group. So three penetration enhancers as enhancing the drug penetration are excellent.