Skin is a complex structured system primarily involved in Transdermal Drug Delivery (TDD). The outer s tratum corneum represents the main barrier to the entrance of external molecules. Nowadays, none of the recognized methods, used for the investigation of penetration processes, is able to give a complete overview of the transport mechanisms involved. Standard protocols are based on the use of human or animal skin samples, which are difficult and expensive to obtain. Here, we present a novel experimental setup to investigate TDD by using Confocal Laser Scanning Microscopy and image analysis. The methodology is based on diffusion experiments of fluorescent-labelled fluids (water, oil, and oil-in-water emulsions), in a model matrix. Using an agarose gel as model for a proof of concept, different penetration efficiencies were observed, suggesting an important role of both chemical composition and fluid microstructure on the transport mechanism. An adequate model system should be used to better mimic the stratum corneum morphology and properties. To this aim, several bicontinuous emulsion gels, obtained from an emulsification process, were preliminary formulated and suggested as model systems to mimic the stratum corneum. In this work, we define the key directions for the development of an innovative approach to study the penetration of formulations through the skin. [ABSTRACT FROM AUTHOR]