Abstract: OBJECTIVE To optimize the extraction process of paeonal from Moutan Cortex by central composite design-response surface methodology. METHODS Paeonal was optimized by central composite design and response surface methodology, which was prepared from Moutan Cortex by steam distillation method. With the ratio of the volume of solvent to the mass of the herb(X₁), the ratio of the volume of solvent to the volume of distillate(X₂) and the mass fraction of sodium chloride into the distillate(X₃) as the independent variables and the yield(Y) as the dependent variable, the binomial and linear equations were fitted to the data, and the resulting equation was used to produce three-dimensional response surface graphs, through which the optimal formulation was predicted, and the best prescription process was verified. RESULTS It showed that the correlation coefficient of second-order quadratic model was higher and the prediction was better(r²=0.987 3, AIC=46.12) than those of linear regression equation. The optimum(the most economical) process for the extraction of paeonol from Moutan Cortex was as follows: X₁=17.97(12.03), X₂=4.42(6.49), X₃=7.97(2.03). The deviation between the result of the best craft verification test and the binomial fitting equation forecast value was acceptable. CONCLUSION Central composite design-response surface methodology is successfully used to optimize the extraction process of paeonol from Moutan Cortex, and the optimized process is reliable for laboratory and industrial production.