AIM To investigate the pharmacological effect of TongXie-YaoFa ng(TXYF) formula on Diarrhea-predominant irritable bowel syndrome (D-IBS) rats.METHODS In a neonatal maternal separation plus restraint stress(NMS+RS) model of D-IBS,male Sprague Dawley rats were randomly divided into two groups(NMS+RS group and TXYF-formula group) with no handlings were used as controls (NH group).Starting from postnatal day 60,rats in TXYF-formula group were administered TXYF-formula for 14 consecutive days while NH group and NMS+RS group were given distilled water.Using short-circuit current technology,we observed 5-HT-induced changes of current across ion channels in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System.RESULTS Under basal conditions,the changes of short-circuit current (Alsc,μA/cm2) induced by 5-HT were similar in NH group and TXYF-formula group,and both higher than NMS+RS group (70.86±12.32 μA/cm2,67.67±11.68μA/cm2 VS 38.8±7.25 μA/cm2,P < 0.01,respectively).When CACC was blocked by DIDS,5-HT-induced Alsc was smaller in NMS+RS group than in NH group and TXYF-formula group,respectively (48.41±13.15 μA/cm2 vs 74.62 ± 10.73 μA/cm2,69.22 ± 11.7 μA/cm2,P < 0.05,respectively).The similar result could be obtained when ENaC was blocked by Amiloride (44.69 ± 12.58 μA/cm2 vs 62.05 ± 11.26 μA/cm2,62.11 ± 12.01μA/cm2,P < 0.05,respectively).However,when CFTR Cl-channel was blocked by DPC,5-HT-induced Alsc did not significantly differ in three groups (42.28 ± 10.61 μA/cm2 vs 51.48 ± 6.56 μA/cm2 vs 47.75 ± 7.99 μA/cm2,P > 0.05,respectively).The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers.CONCL USION TXYF-formula can regulate the Cl-and HCO3-secretion of colonic mucosa via CFTR Cl-channel,Cl-/HCO3-exchanger,NBC and NKCC co-transporters.