Menthyl nicotinate is a new multifunctional, sensory active ingredient that activates the microcirculation of the skin. It has been proven to be effective as an antioxidant, antipollutant, detoxifying and protective agent. This in vitro study on a reconstructed human epidermis (RHE) model investigates menthyl nicotinate’s fast penetration kinetics through the skin, and how its subsequent hydrolysis releases menthol and niacin (vitamin B3) within 24 hours of its application. The total release of niacin was analyzed at different time points, and the release curve was plotted. Niacin slow diffusion in the underlying skin layers, where it interacts with the epidermal and dermal biological structures, was also studied. Such time-dependent release of niacin and menthol, in an equimolar ratio, prevents the niacin-flush effect that is usually observed with other nicotinate-based formulations. It also allows menthyl nicotinate to gradually interact with skin thermoreceptors, alone or in combination with other sensory agents, to provide a characteristic pleasurable and modulated effect.