OBJECTIVE： To optimize the preparation technology of Compound antipyretic suppository and establish a method for quality control of the suppository. METHODS： The orthogonal test was adopted to optimize the preparation technology of Compound antipyretic suppository with the amount of polysorhate-80， the ratio of lanolin to mixed fatty acid ester， bath temperature and stripping time as factors， using the comprehensive score of appearance， in vitro release rate of isoimperatorin as index. Then pH， hardness， weight difference， melting time of the suppository prepared by optimized technology， the content and in vitro drug release of isoimperatorin were investigated to establish the method for quality control. RESULTS： The optimal technology was that the content of polysorhate-80 was 1.5％； the ratio of lanolin to mixed fatty acid ester was 1 ∶ 15； the bath temperature was set at 50 ℃ and the stripping time was 15 min. The average comprehensive score of validation test was 98.52 （RSD＝1.86％，n＝3）. The pH， hardness， weight differences and melting time of prepared suppository were 7.12， 10.5-12.5 N， 1.7％-5.6％ and 10-15 min； average content of isoimperatorin was 98.93％ and it released completely within 24 h. CONCLUSIONS： The optimized preparation technology is reasonable and feasible， and prepared suppository is in line with the quality requirements.