Da-Cheng-Qi decoction (DCQD) is composed of dahuang, houpu, zhishi and mangxiao, while Xiao-Cheng-Qi decoction (XCQD) just contains dahuang, houpu, and zhishi. A validated high-performance liquid chromatographic (HPLC) method was developed for the determination and pharmacokinetic comparison of rhein in rats. It was performed on a reversed-phase C(18) column (150 x 4.6 mm) with a mobile phase of methanol and 0.2% acetic acid (89:11, v/v) and ultraviolet detection at 254 nm. The assay was linear over the range 30-3000 ng/mL (r(2) = 0.9991), with mean percentage recovery of 101.4%. The RSD of intra- and inter-day precision were less than 3.0%, with accuracy in the range 96.8-102.5% for each of the concentrations tested. Following oral administration, rhein plasma levels revealed curves characterized by peaks at 20.5 and 30.1 min corresponding to dosages of 15 mg/kg (XCQD) and 20 mg/kg (DCQD) at mean concentrations of 1184.67 and 1814.27 ng/mL, respectively. The half-lives of rhein from XCQD and DCQD were 45.3 and 139.6 min, respectively. AUC(0-12h) of rhein after oral dosage with XCQD and DCQD were 3435.68 and 5382.25 microg/L h, respectively. The pharmacokinetic parameters may be used to guide the clinical prescription compatibility of traditional Chinese prescriptions related to dahuang and mangxiao.