Abstract: OBJECTIVE To optimize the composition of cream matrix, in order to get the best Compound Triamcinolone Acetonide Acetate cream with good appearance, good usability and good stability. METHODS The composition of the Compound Triamcinolone Acetonide Acetate cream was determined by using D-optimal mixture design method, which was based on the centrifugal stability, cold stability, heat stability, particle size, ductility, appearance and cleaning. RESULTS The best prescription of Compound Triamcinolone Acetonide cream was:stearic acid 8.3 g, glycerol monostearate 7.6 g, white vaseline 9.5 g, liquid paraffin 8.1 g, twelve alkyl sodium sulfate 1.1 g, glycerol 7.5 g and water 57 g. CONCLUSION The Triamcinolone Acetonide Acetate cream made according to the compound prescription preparation have good stability, and it is easy coating.