Transdermal drug delivery system has been limited to small and lipophilic drugs because skin has the intrinsic function to protect the body preventing entry of the external species into the body. In this thesis, two physical methods were studied to overcome the skin barrier in the controlled breakage of the skin barrier and to deliver macromolecules-based drugs through the skin; (1) polysaccharide dissolving microneedles and (2) micro thermal skin ablation. Polysaccharide dissolving microneedles system was designed to break the skin barrier in a minimized size with the mechanically poor material, to release them into skin with the dissolution of microneedles, and to deliver human growth hormone into the living hairless rats. Micro thermal skin ablation was designed to fabricate the device generating the energy impact with the basis of arc discharge, to transfer the energy impact on the skin, to remove stratum corneum selectively with three-dimensionally controlled manner, and to deliver hydrophilic macromolecules through skin.