Abstract: AIM　To quatitatively disclose the relationship between activity and structure of a new class of COX-II inhibitors containing dialkylphenyl-linked heterocyclic moieties. METHODS AND RESULTS Seventeen COX-II inhibitors from literature as a training set were investigated with the aim of developing a 3D-QSAR model using comparative molecular field analysis (CoMFA). To reveal the pharmacophoric pattern, several modes of superimposition were explored. The significant model shows a higher ability to explain and predict the activity of COX-II inhibitors, with the cross-validation R_CV²=0.718, non cross-validation R²=0.992, F=260.624, and SEE (standard error of estimate)=0.072. Three compounds were selected as a predicting set, the low deviations of calculated values from the measured ones suggesting a powerful predictive ability of the model. CONCLUSION　The 3D-QSAR explains the dependence of COX-2 inhibition upon the structures of the compounds. Some structure information for design of new COX-II inhibitors with higher activity has been given.