In the present study, chitosan membranes capable of imitating permeation characteristics of diclofenac diethylamine across animal skin were prepared using cast drying method. The effect of concentration of chitosan, concentration of cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design. Taguchi design ranked concentration of chitosan as the most important factor influencing the permeation parameters of diclofenac diethylamine. The flux of the diclofenac diethylamine solution through optimized chitosan membrane (T9) was found to be comparable to that obtained across rat skin. The mathematical model developed using multilinear regression analysis can be used to formulate chitosan membranes that can mimic the desired permeation characteristics. The developed chitosan membranes can be utilized as a substitute to animal skin for in vitro permeation studies.