AbstractPeriplocin is an important compound of Cortex Periplocae, which shows poor absorption when administered orally. The effective intestinal permeability of periplocin was investigated using single‐pass intestinal perfusion technique in male Wistar rats. SPIP was performed in rat jejunum. The samples of perfusate were collected at the designated time points after rat intestinal perfusion and analyzed by HPLC. The specificity of this method was demonstrated by the absence of interference of the drug peak with the intestinal sac artifacts and the components of the KRB solution. Recovery studies, as well as the intra‐day and inter‐day variations, were within statistical limits. This technique was applied to the study of the intestinal absorption of periplocin. The determined fraction absorbed (Fa) of periplocin was 0.151 ± 0.072 (n = 6) at a concentration of 6 µg/mL; the absorption rate constant (Ka) was 0.0102 ± 0.0039/min and the effective permeability coefficient (Peff) was 0.0021 ± 0.0012 cm/min. These data suggest that periplocin has high permeability and might be absorbed in rat intestine. Copyright © 2007 John Wiley & Sons, Ltd.