A study of the transdermal delivery of Cyclosporine A by atmospheric plasma irradiation was realized on the epidermal layer of the Hairless Yucatan micropig. Drug flux and the amount of drug penetrated through the skin were determined by a Franz cell diffusion experiment. After treatment of the skin by atmospheric plasma jet or microplasma dielectric barrier discharge, an increase in the permeability of the skin was observed. The authors did not observe drug penetration for samples that were not treated with plasma. There was no significant difference between treatments of skin by plasma jet or microplasma dielectric barrier discharge. Drug flux increased to its maximal value up to 3 h after the drug application, and then it decreased. This phenomenon could indicate a temporal effect of plasma on skin. A pharmacokinetic two-compartment model was developed to estimate the possibility of using plasma drug delivery of Cyclosporine A in medical praxis. Our model showed that it is possible to use this technique if a suitable treatment area and concentration of applied drug are chosen.