Abstract: OBJECTIVE The mechanism of Glycyrrhizae's incompatibility with "zao-ji-sui-yuan"(Sargassum， Euphorbia pekinensis， Euphorbia kansui and Daphne genkwa) was explored by assessing intestinal P-glycoprotein (P-gp) activity in vitro. METHODS Ussing-chamber technique was used to determine intestinal secretory function. Rhodamine123 (R123) was used as an indicator of P-gp activity. RESULTS Glycyrrhizae could significantly promote the secretion of R123. In the present of Sargassum， Euphorbia pekinensis and Daphne genkwa， the promotion effect of Glycyrrhizae was significantly suppressed. CONCLUSION P-gp activity can be significantly induced by Glycyrrhizae. The promotion effect of P-gp activity induced by Glycyrrhizae was antagonized by Sargassum， Euphorbia pekinensis and Daphne genkwa， which might lead to the reduction of toxic components pumping out and then aggravated intestinal tissue injury. These results indicated that when Glycyrrhizae combined with some toxic traditional Chinese medicine， change of the intestinal P-gp activity might cause the "contrary effects".