Aim Paeoniflorin (PF) and albiflorin (AF) are the main components of total peony glucosides(TPG), which has been widely used as the valuable monoterpene glycosides in Paeonia lactiflora Pall and have many biological activities such as antiinflammatory, antihypertension and antioxidation effects.In this study, the pharmacokinetic interaction and possible interaction mechanism among PF and AF and TGP were conducted and investigated.A sensitive and specific ultra highperformance liquid chromatographytandem mass spectrometry method (UPLCMS) was successfully developed and validated for simultaneous quantification of PF and AF in rat plasma after intragastric administration and the comparative study of pharmacokinetics for PF and AF in different combinations.The combinations of PF (80 mg · kg1), AF (14 mg · kg1), coadministration of PF (80 mg ·kg1) and AF (14 mg · kg1), TPG (PF 80 mg · kg1) and TPG (AF14 mg · kg1) were orally administrated to rats respectively.Chromatographic separation was performed on a ZORBAX Eclipse plus C18 column using 0.2%formic acidmethanol (79∶21, V/V) as mobile phase.The calibration curves were linear in ranges of 0.5 ~ 1000μg · L1.The results indicated that the main pharmacokinetic parameters including AUC, MRT and t1/2 between the single ingredient (PF and AF) and TPG had significant difference (P < 0.05 or P < 0.01).The different pharmacokinetics data implied that the multiple active components of TPG resulting some potential drugdrug interactions, which may promote the absorption and decease the elimination of PF and AF.Our results could be helpful for further investigation of the interaction mechanism of PF and AF.