Abstract: OBJECTIVE To investigate the effect of Tongxie Yaofang decoction on intestinal hypersensitivity in diarrhea predominant irritable bowel syndrome(D-IBS) rats with liver-stagnation and spleen-deficiency pattern.METHODS D-IBS rat model of liver depression and spleen deficiency was established by perfusing Senna Folium and chronic restraint, then to observe the effects of Tongxie Yaofang decoction on the related indexes of HPA axis corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), cortisol(CORT), p38 MAPK, MSK1 phosphate and cyclic-AMP response binding protein(CREB) expression in colon tissues.RESULTS Tongxie Yaofang decoction could reduce the contents of CRH, ACTH, CORT, and inhibit p38 MAPK, MSK1 phosphorylation and CREB protein expression in colon tissue of D-IBS rats with liver depression and spleen deficiency type, especially in the high dose group of Tongxie Yaofang decoction(P<0.05 or P<0.01).CONCLUSION Tongxie Yaofang decoction can anti-abdominal pain effect on D-IBS rats of chronic restraint and liver stagnation and spleen deficiency type after oral administration of Senna Folium. The mechanism is related to down-regulation of p38 MAPK, MSK1 phosphorylation and CREB protein expression, and inhibition of HPA axis hyperfunction.