Abstract: A series of 2’-hydroxychalcones was synthesized and screened for their in vitro inhibitory effects on PGE2 production from RAW 264.7 cells induced by LPS. Structure–activity relationship study suggested that inhibitory activity of PGE2 formation was governed to a greater extent by the substituent on B ring of the chalcone template, and most of the active compounds have at least two methoxyl or benzyloxyl groups on B ring. The relationship between chalcone structures and their PGE2 inhibitory activity was also interpreted by docking study on cyclooxygenase 2.