Objective To optimize the formulation and process of liposome gel of total alkaloids of Sophoras Flavescentis Radix; To prepare the liposome gel of total alkaloids of Sophoras Flavescentis Radix and study its release mechanism.Methods Matrine liposomes was prepared by using film dispersion method; With entrapment efficiency and medicine loading as indexes, acid dye colorimetric method was used for the determination of matrine content in liposomes. Orthogonal design was used to optimize the formulation and the optimal formulation of liposomes was selected. Poloxamer-407 was set as the substrate preparation of matrine liposome gel. The transdermal rate of medicine gel and medicine liposome gel was investigated.Results Obtained through formulation and technology optimization of liposomes formation uniform, particle size was in the range of 100 nm to 400 nm, entrapment 74%, loading 26%. Preparation of liposome gel was transparent semisolid. In vitro results showed, cumulative release dose of matrine hydrogel was 6.34 mg/cm2 within 48 h; cumulative release doses of liposome gel of total alkaloids of Sophoras Flavescentis Radix was 6.97 mg/cm2 within 48 h; cumulative volume, steady-state penetration rate through skin and 48 h volume in the skin of the latter were significantly improved compared with that of the former. Conclusion Optimum preparation is reliable and practical. Liposome gel of total alkaloids of Sophoras Flavescentis Radix made by the preparation is with high quality, which can effectively delay the medicine release rate, increase the volume of medicine in human body.