Aspartic protease SASPase in the skin of mice with atopy-like dermatitis (dermatitis mice) has been found using proteome analysis in our previous study. In this study, we examined whether SASPase was involved in itching in mice with atopic dermatitis. The expression of SASPase was increased in the skin of dermatitis mice, compared with healthy mice. An intradermal SASPase, but not heat-inactivated SASPase, elicited itch-related responses. SASPase was distributed in epidermis, especially granular layer and stratum spinosum. In the skin of dermatitis mice, the peripheral nerves were elongated into the epidermis. Interestingly, SASPase digested nerve repellent factor expressed in epidermis. These findings suggest that SASPase is one of itch mediators and also may play an important role on the elongation of peripheral sensory nerves.