A Quantitative Structure Activity Relationship (QSAR) study of 3, 4-Diaryloxazolones has been performed to evaluate the descriptors responsible for the COX-2 inhibitory activity of the molecules. The molecular modeling studies were performed using CS Chem.Office 2005 molecular modeling software ver. 9.0. Allinger’s MM2 force field and semiempirical AM1 (Austin Model 1) Hamiltonian method (MOPAC module) were used to minimize the energy and energy minimized geometry was used to calculate 40 different descriptors. Stepwise multiple linear regressions were performed to obtain the QSAR models. An analysis of the QSAR models was performed to select the best model which suggests that steric and electronic parameters of the molecules are highly correlated with COX-2 inhibitory activity.