OBJECTIVE: To prepare paeonol-HP-β-cyclodextrin (PAE-HP-β-CD) inclusion compound and to optimize its prescription technology. METHODS: PAE-HP-β-CD was prepared by freeze drying method and validated. Using inclusion rate as index, main drug-accessory ratio, inclusion time, inclusion temperature and stirring speed as factors, the preparation technology was optimized by central composite design-response surface methodology. RESULTS: Prepared PAE-HP-β-CD underwent phase transformation. The optimal inclusion technology was as follows as main drug-accessory ratio of 3.39 ∶ 1, inclusion temperature of 50 ℃, inclusion time of 3.2 h, stirring speed of 350 r/min. Relative error between measured value (87.46%) and predicted value (89.12%) of inclusion rate was 1.86% (n=6). CONCLUSIONS: PAE-HP-β-CD inclusion compound is prepared successfully, and its prescription technology is stable and feasible.