Prochlorperazine (PCPZ) is used as a drug of first choice to treat opioid-induced nausea and vomiting. To examine the feasibility of the development of a transdermal drug delivery system for PCPZ, we performed an in vitro skin permeation study with hairless mouse skin. When the concentration of L-menthol in the hydrogel was 0—0.5%, the PCPZ flux was small; on the other hand, the flux was increased remarkably when the L-menthol concentration was higher than 1%. The optimal formulation of hydrogel would be contained 20% isopropanol (IPA), 10% N-methyl-2-pyrrolidone (NMP), 2% L-menthol and 1% PCPZ. The strong inhibitory effects to stereotyped behavior were observed at 4 h after administration of PCPZ hydrogel, and the efficacy was sustained for at least 8 h after the administration in mice in vivo. Thus, it was considered that PCPZ was delivered to brain via systemic circulation by the administration of PCPZ hydrogel.