Abstract: A group of p-amino-diphenyl ether analogues were tested for their activities toprofong the pentobarbital sleeping time in mice and to inhibit the demethylation of p-nitro-anisolecatalyzed by untreated mouse hepatic microsomes in vitro,The stepwise multiple regression analyseswere used to obtain the quantitative structure-activity relationships between the activities of inhibitingcytochrome P-450 in vitro or in vivo for the analogues and their quantum chemical indexes. The resultsshowed that the inhibiting activities both in vitro and in vivo were correlated with the energy level of thelowest unocupied molecular orbital(E_tuMO) ,the nucleophilic superdelocalizabilities of the nitrogen(S_N(N))and the oxygen(S_N(0)).The inhibiting activities of the analogues to cytochome P- 450may mainly come from their ability to form cytochrome P-450 metabolic intermediate complex.