The mathematical model of the herb leaching process is presented in this paper based on the mass transfer principle. At the same time, the process system engineering methodology is applied to study the herb leaching process in order to improve the operating conditions and the yields of effective compounds. The modification parameters in the model are predicted using parameter estimation technique to make the model calculated values agree with the experimental data. A case study for the angelica leaching process was presented. The simulation results show a perfect matching between the calculated values with the experimental data. The effects of different operating conditions on the yield of effective compounds in the herb leaching process are also investigated applying the simulation study. Furthermore, the optimal operating condition is obtained to maximize economic profit. The results also indicate the extended application prospects of simulation and optimization technology in the modernization of Chinese traditional herb leaching production.