OBJECTIVE： To establish a method for the concentration determination of apatinib mesylate in plasma of rats， and to investigate the effects of single and multiple administration of Wuzhi capsules on the pharmacokinetic behavior of apatinib mesylate in rats. METHODS：  LC-MS/MS method was used to detect the plasma concentration of apatinib mesylate in rats. Using carbamazepine as internal standard， the determination was performed on Waters XBridge BEH C18 column with mobile phase consisted acetonitrile-0.1％ formic acid solution （45 ∶ 55，V/V） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃. The temperature of injector was 15 ℃， and the sample size was 2 μL. ESI was used for positive ion scanning in MRM mode. The ion pairs m/z used for quantitative analysis were 398.1→212.1 （apatinib mesylate） and  237.2→194.2 （internal standard）. The rats were randomly divided into control group Ⅰ， observation group Ⅰ， control group Ⅱ， observation group Ⅱ， with 6 rats in each group. Control group Ⅰ were given single administration of apatinib mesylate intragastrically （50 mg/kg， similarly hereinafter）. Observation group Ⅰ was given Wuzhi capsules intragastrically （450 mg/kg， similarly hereinafter）， and then 10 min later given apatinib mesylate intragastrically. Control group Ⅱ was given normal saline intragastrically， once a day， for consecutive 7 d， and then were given single administration of apatinib mesylate. Observation group Ⅱ was given Wuzhi capsules intragastrically， once a day， for consecutive 7 d， and then 10 min later were given single administration of apatinib mesylate. The blood samples were collected from intraocular canthus vein plexus and determined 0.25， 0.5， 1.0， 2.0， 2.5， 3.0， 4.0， 6.0， 8.0， 12.0， 24.0 h after intragastric administration， respectively. Pharmacokinetic parameters were apatinib mesylate were calculated and compared among those groups by using DAS 2.1 software and t-test. RESULTS： The linear range of apatinib mesylate were 2-2 000 ng/mL. The lower limit of quantitation was 2 ng/mL. RSDs of intra- day and inter-day were all lower than 10％， and the accuracy were 94.93％-104.68％. Matrix effect did not affect the quantitative analysis of the substance to be measured. Compared with control group Ⅰ， cmax， AUC0-24 h and AUC0-∞ of observation group Ⅰ were increased significantly， CLZ was decreased significantly （P＜0.05）. Compared with control group Ⅱ， AUC0-24 h and AUC0-∞ of observation group Ⅱ were increased significantly， and CLZ was decreased significantly （P＜0.05）. Compared with observation group Ⅰ， AUC0-24 h and AUC0-∞ of observation group Ⅱ were decreased significantly （P＜0.05）. CONCLUSIONS： Established LC-MS/MS method is sensitive and specific， and can be used for the concentration determination of apatinib mesylate in plasma of rats. Wuzhi capsules can influence in vivo pharmacokinetic behavior of apatinib mesylate in rats. The effect of multiple administration of Wuzhi capsules is weaker than that of single administration.