Meissner corpuscles are the fast adapting type I (FA-I) mechanoreceptor that locates at the dermal papillae of skin. The Meissner corpuscle is well known for its complex structure, consisting of spiral axons, lamellar cells, and a collagen capsule. Fluorescent microscopy has become a convenient method for observing the Meissner corpuscle and its inner structure. This method requires preparing samples with fingertip cross-sections and performing antibody staining before observation. Various kinds of microscopy can be used for observation, such as confocal microscopy, transmission electron microscopy (TEM), or scanning electron microscopy (SEM). Although the anatomical shape, distribution, and components of Meissner corpuscle are recognized, they have been mostly determined from observations of fixed tissues. Therefore, knowledge of mechanical transduction is limited by the lack of in vivo experiments and individual differences among samples. In this study, we propose a novel less invasive imaging method that incorporates a staining technique with lipophilic carbocyanine DiOC(16)(3) and two-photon microscopy. This combination allows us to repetitively observe the Meissner corpuscle in a living mouse.