The development of microfluidic culture technology facilitates the progress of study of cell and tissue biology. This technology expands the understanding of pathological and physiological changes. A skin chip, as in vitro model, consisting of normal skin tissue with epidermis and dermis layer (full thickness) was developed. Polydimethylsiloxane microchannels with a fed-batched controlled perfusion feeding system were used to create a full-thick ex-vivo human skin on-chip model. The design of a novel skin-on-a-chip model was reported, in which the microchannel structures mimic the architecture of the realistic vascular network as nutrients transporter to the skin layers. Viabilities of full-thick skin samples cultured on the microbioreactor and traditional tissue culture plate revealed that a precise controlled condition provided by the microfluidic enhanced tissue viability at least for seven days. Several advantages in skin sample features under micro-scale-controlled conditions were found such as skin mechanical strength, water adsorption, skin morphology, gene expression, and biopsy longevity. This model can provide an in vitro environment for localizing drug delivery and transdermal drug diffusion studies. The skin on the chip can be a valuable in vitro model for representing the interaction between drugs and skin tissue and a realistic platform for evaluating skin reaction to pharmaceutical materials and cosmetic products.