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The present study was designed to develop a suitable matrix type transdermal drugs deliver system (TDDS) of Asenapine using various polymers like Ethyl cellulose (EC) and Hydroxy Propyl Methyl Cellulose (HPMC) and natural permeation enhancers. In vitro drugs release studies were performed by using a modified USP type II dissolution apparatus. In vivo pharmacokinetics studies of Asenapine TDDS were done to check the efficacy of transdermal formulation in rabbits. Rota rod test and behavioral observations were carried out to find out the tranquilizing efficacy of TDDS comparable to oral marketed formulation in mice. The better bioavailability data of transdermal patches also proves advantage of transdermal formulation as compared to conventional formulation.