As the results of a study on an invasive stimulation receptor, it is found out that this stimulation receptor exists in epidermal cells, etc. and changes are observed in intracellular calcium concentration depending on the state of this stimulation receptor. Namely, a method of detecting a skin stimulation effect based on the relation between the stimulation effect of a test substance which are in contact with epithelial cells such as epidermal cells and an increase/decrease in calcium ion concentration in the epithelial cells.