The purpose of this work was to develop once a week matrix-type transdermal drug delivery system containing lisinopril with different concentrations of chitosan by the solvent evaporation technique without any penetration enhancers. Various concentrations of chitosan films prepared with lisinopril were evaluated. The physicochemical compatibility of the drug and the polymers was studied by Infrared spectroscopy and Differential Scanning Calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. In-vitro permeation studies were performed in cadaver skin and rat skin by using modified Franz diffusion cells. The results followed Higuchi kinetics (R2 = 0.98), and the mechanism of release was diffusion mediated. Based on physicochemical and in-vitro skin permeation studies, patches coded as CL-2 were taken for further studies. Accelerated stability studies performed according to ICH guidelines confirmed that there was a very low degradation rate constant was observed. In-vivo skin irritation studies confirmed there were no signs of reactions were perceived on the skin of albino rats after 7 days. The results of this study indicate that the chitosan based matrix films of lisinopril hold potential for prolonged transdermal drug delivery.