After tail loss in the African gecko Lygodactylus capensis (Smith, 1949) a new tail is regenerated, including caudal adhesive pads. The axial skeleton of the regenerating tail consists in an elastic cartilaginous tube replacing the original vertebrae that allows interacting with the substrate like in the original tail. The formation of adhesive setae has been analyzed using transmission and scanning electron microscopy coupled to immunolabeling for Corneous Beta Proteins. During progressive stages of epidermal differentiation new setae are developed at stage 4 of the shedding cycle and contain Corneous Beta Proteins. These structural proteins are faintly localized in the Oberhäutchen but are abundant in the beta-layer, indicating that the two epidermal layers have a different protein composition. The setae originate from the growth of Oberhäutchen spinulae into the cytoplasm of clear cells and the latter produce a thick fibrous meshwork of keratin and other unknown proteins localized around the growing setae. This cytoskeleton likely allows molding tail setae like for digital setae. A graded development of setae is observed from the base to the tip of regenerated pads and from the periphery to more central areas. The terminal end of the setae is subdivided into numerous filamentous spatulae that increase the adhesion contact. Sensory boutons are frequently detected at the margin of tail scales and adhesive pads, likely improving compliance with the substrate. The present study indicates that tail regeneration is a convenient experimental model to analyze adhesive setae formation, microstructures that allow to these lizards climbing vertical and arboreal substrates.