To optimize the matrix formulation of traditional Chinese medicine(TCM) gel plaster for removing fetal toxin and investigate its in vitro release and permeation properties.Methods:The optimized matrix formulation of gel plaster was determined using D-optimal mixture design，with adhesion，initial adhesion，and cohesion as indices.A high-performance liquid chromatography(HPLC) method was established to determine the active component geniposide(GP).The Franz diffusion cell method was used to study the in vitro release and permeation of GP，followed by model fitting.Results:The optimized matrix formulation of TCM gel plaster for removing fetal toxin contained sodium polyacrylate 700，aluminum glycinate，tartaric acid，glycerin，polyvinyl pyrrolidone 90，and distilled water(6:0.4:0.4:30:4:49.2).The cumulative release rate of GP was(81.15±3.93)% in 24 h.The cumulative permeation rate of GP was(15.30±4.87)% in 24 h.The in vitro release of GP was in accordance with the first-order equation，and the release mechanism was a synergic process of dissolution and diffusion.The in vitro permeation was close to the zero-order equation，and the permeation mechanism was dissolution.Conclusion:The gel plaster prepared under the optimal matrix formation shows an ideal adhesion.The drug release rate of GP is higher than the permeation rate，which means the skin barrier plays a speed-limiting role.