Abstract: AIM　To study the SARs of 5,6-diaryl-2,3-dihydro-1-pyrrolizinone derivatives to provide information for the design of new structural compounds. METHODS AND RESULTS　Three dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed by Apex-3D. CONCLUSION The antiinflammatory activities of 5,6-diaryl-pyrrolizinones were related to the global hydrophobicity and volume, the properties of the group at 1-position of pyrrolizinone ring and the two secondary sites; improved the π-electronic density of the group at 1-position of pyrrolizinone ring and lowered the global hydrophobicity and the volume of p-substituent of the phenyl ring at 6-position of pyrrolizinone contributed to the antiinflammatory activities of the title compounds.