Histological alterations in the skin and hair follicle of mice were evaluated as a result of the application of gel and cream formulas containing papain as a harmless treatment for hirsutism. Papain is a proteolytic enzyme and it has been used in pharmaceutical, cosmetic and nutrition areas. The purpose of this study was to evaluate the efficacy of a depilatory product, through histological analysis using light microscopy. Gel and cream formulas containing papain were developed and daily applied on the back of two groups of mice for 31 days. The depilatory effect of the gel formula applied on the first group was less evident. The second group treated with the cream formula presented an intensive depilatory effect; the morphometrical analysis showed dilation of about 55% of the hair follicle lumen and an increase of the thickness of epidermis. Papain cream had a significantly higher depilatory effect than the papain gel.