Chronic gastritis (CG) has become a major threat to human health. Banxia Xiexin Decoction (BXXXD) has been used clinically to treat gastritis by acting on the spleen and stomach for thousands of years. Baicalin, wogonoside, liquiritin and liquiritigenin are the main bioactive flavonoids of BXXXD. A rapid, sensitive and selective HPLCtriple quadrupole (TQ)-MS/MS method was developed to simultaneously quantify the four flavonoids in rat plasma in this study. With salidroside as internal standard (IS), plasma samples were extracted and separated on a Welch HPLC XB-C 18 column (2.1 Â 50 mm, 1.8 μm) using gradient elution. The optimized gradient of the mobile phase consisted of water (containing 0.1% formic acid) (A) and methanol (B) was used.Detection was implemented in multiple reaction monitoring mode with an electrospray negative ionization source. The comparative pharmacokinetics of four analytes in normal and CG rats after oral administration of BXXXD or its different compatibilities were first investigated. The results indicated that the pharmacokinetic behaviors of analytes were obviously changed in CG rats. From the comparison between the whole prescription group and the compatibility groups, it was found that the pharmacokinetic behavior of analytes also changed to some extent. The pharmacokinetic alterations of analytes might be due to the pathological conditions of CG.