OBJECTIVE: To establish a method for the determination of emodin, rhein and calycosin in rat plasma, and to study pharmacokinetics of Qixue extract in rats. METHODS: LC-MS/MS method was adopted. The determination was performed on Thermo C18 column with mobile phase consisted of acetonitrile-0.1% formic acid solution (gradient elution), and flow rate of 0.2 mL/min. The column temperature was set at 30 ℃, and sample size was 20 μL. The quantitative ions were emodin m/z 269.7→226.1, rhein m/z 283.7→239.9, calycosin m/z 283.5→268.5 and diazepam m/z 285.0→154.1. The blood concentration of samples from orbital cavity of 6 rats were determined 0.08, 0.17, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 h after intragastric administration of Qixue extract 8.91 g/kg (by clinical dosage). DAS 1.0 pharmacokinetic software was employed to calculate pharmacokinetic parameters. RESULTS: The linear ranges of emodin, rhein and calycosin were 1.988-198.8 ng/mL (r=0.998 8), 2-200 ng/mL (r=0.998 8) and 2.092-209.2 ng/mL(r=0.998 5), respectively. RSDs of precision and accuracy tests were all less than 7.78% (n=5). The recoveries were 92.13%-102.23%, 90.15%-93.67% and 90.33%-104.63% (n=5), respectively. RSDs of stability tests were all less than 6.54% (n=3). The pharmacokinetic parameters of emodin, rhein and calycosin were as follows as t1/2 were (1.95±0.53), (3.55±1.25), (4.21±1.14) h; AUC0-12 h were (192.67±40.58), (93.67±20.26), (608.41±108.36) μg·h/L; cmax were (89.56±12.87), (31.84±10.58), (300.56±50.57) μg/L; tmax were (0.50±0.00),(0.75±0.23),(1.00±0.00) h; CL were (5.45±1.12), (2.09±0.47), (10.01±1.25) L/(h·kg) (n=6), respectively. CONCLUSIONS: Established method is highly sensitive, accurate and reliable. The elimination process of emodin, rhein and calycosin are first-order elimination, which is in line with two-compartment model.