Skin is interface between inside of the body and dried environment. Stratum corneum, outermost layer of skin, maintains physical barrier to prevent dehydration and invasion of exogenous substrate. Morphology of stratum ocnruem sometimes compared to “brick-mortal” model. Keratinocyte corresponds to “brick” and intercellular space corresponds to “mortal”. Intercellular space is filled by lipids, such as ceramides, cholesterol and free fatty acids. Those lipids form regular arrangement, so called “lamellar structure”. Lipid lamellar structure is considered to bear the main barrier function of skin. There are two kinds of lamellar structure of intercellular lipids. The periodicity of long lamellar structure is about 13 nm and that of short lamellar structure is about 6 nm. The lateral packing of lamellar structure is known as orthorhombic and hexagonal packing. There exists several phase transition of intercellular lipids such as liquidization of orthorhombic packing, formation and liquidization of high-temperature and liquidization of long and short lamellar. Those phase transition was affected by the administration of components of topical and transdermal formulation. Change in thermotropic behavior of intercellular lipids might be a key factor of promoting activity of skin permeation enhancement of topical and transdermal formulation. To develop effective formulation, observation of phase transition is important to evaluate formulation components.