Rhei Rhizoma, also named as rhubarb or Da Huang, has been used widely in oriental traditional medicine in treating constipation and edema. However, though much affection has been paid to the make of components on pharmaceutical mechanisms, few studies have been conducted to reveal chemical and physical mechanism of these effects. Studies have shown that diarrhea causes imbalance of chloride and sodium ion movements via epithelium, we wondered if similar mechanism may apply to Rhei Rhizoma, a herbal drug which has been used to treat constipation in oriental medicine for thousands of years. The measurement of short-circuit current (Isc) has been used widely to estimate the ion transportation between mucosal and serosal side of epithelium. In this study, we used Ussing chamber technique to examine the alternation in membrane potential and short-circuit currents. The result shows, at default, the Isc of frog skin we used was at 59.23¡Ó5.58£gA/cm², and the conductance was at 1.11¡Ó0.50£gA/cm²¡EmV. The lnjection of 1ml RRE to mucosal side of the frog skin leaded to a 90% elevation of the Isc. Followed by the application of Amiloride (sodium channel inhibitor) and Chlorothiazide (chloride channel inhibitor) to mucosal side of the epithelial skin, the observed Isc were then reduced 136% and 33% respectively. If RRE were applied after the adding of Amiloride or Chlorothiazide to the frog skin, then the Isc of the skin elevated only 24% and 70% respectively. These results show that Rhei Rhizoma Extract (RRE) significantly increases Isc upon application to the mucosal side of the skin epithelium. Amiloride and Chlorothiazide will both inhibit the Isc induced by RRE, indicating activation of chloride channel and Amiloride-sensitive sodium channel of the epithelial tissue by RRE. After the regular Ringer solution used in the preparation was replaced by Na-free and Cl-free Ringer solution, the inhibition of Isc by RRE application could still be observed although the inhibition was trivia. These results indicate that RRE acts dominantly on mucosa side of the epithelium and can be used to enhance sodium transport and to stimulate the secretion of Cl- in the epithelium.