Cyclooxygenase (COX), a key enzyme playing crucial role in prostaglandin biosynthesis in Rheumatoid arthritis (RA) inflammation. For targeting COX-2 isoform, it is therefore interesting to design new molecule scaffolds with reduced side effects at gastric and renal levels. QSAR can modify the molecular structures for achieving the desired molecule with the proposed property, without experimental measurement. In the current study, we extend a published work that had been investiged the of 3, 5-diphenyl-2thioxo imidazolidin-4-ones derivatives as cyclooxygenase inhibitors. In this report, QSAR and regression analysis were used to predicate the cyclooxygenase inhibition activity of these derivatives. Moreover the cyclooxygenase inhibition activity for these molecules that was obtained experimentally is compared with the calculated ones. The cyclooxygenase inhibition activity of some of newly postulated 3, 5-diphenyl-2thioxo imidazolidin-4-ones derivatives showed a pronounced cyclooxygenase inhibition activity. QSAR and regression equations were useful in predicating the biologic activity of the old and postulated molecules with good validity.