In order to prove whether downregulation of COX-2 (Cyclooxygenase-2) could modulate the epithelialmesenchymaltransition (EMT) of breast cancer, celecoxib and siRNA were respectively used to inhibit COX-2function and expression in MDA-MB-231 cells. The EMT reversal effect in the RNAi treated group was betterthan that of the celecoxib group while there were no obvious differences in the medium PGE2 levels betweenthe two groups. The results show that COX-2 pathways may contribute considerably to EMT of breast cancercells, partially dependent on the PGE2 cascade. Akt2, ZEB2 and Snail were measured to clarify the underlyingmechanisms of COX-2 on EMT; COX-2 may modulate EMT of breast cancer by regulating these factors. Thisfinding may be helpful to elucidate the mechanisms of selective COX-2 inhibitor action in EMT modulation inbreast cancer.