Abstract: OBJECTIVE To optimize the matrix formula and technological parameter of Huangyu Ointment by using the central composite design-response surface methodology. METHODS Single factor experiment and orthogonal experiment were used to optimize the extraction process and matrix composition with total flavonoids, baicalin, emodin and berberine hydrochloride as index components. With the sensory score and stability constant of ointment as evaluation indices, chose the best matching of glycerinum, glycerin monostearate and caprylic/capric triglyceride(GTCC) by central composite design-response surface methodology. RESULTS The optimum formula consisted of 13.3% propylene glycol, 20.55% glycerinum, 7.75% glycerin monostearate and 23.78% GTCC. CONCLUSION According to the single factor, orthogonal test and central composite design-response surface methodology, the new formula of Huangyu Ointment have acquired with uniform and delicate appearance, and it have appropriate viscosity and good stability.