Abstract: OBJECTIVE To study the therapeutic effect of Changkang Granules in rat with irritable bowel syndrome with Diarrhea （IBS-D) and investigate its mechanism． METHODS The model for IBS-D was established by colorectal distention daily in the neonatal rats between postnatal 8 and 21 days. Sixty SD rats were divided into the normal control group，the model group，positive control group，high-dose，middle-dose，low-dose Changkang Granules group．The treatment lasted for 30 days． The threshold of abdominal withdrawal reflex(AWR) during rectal distension was evaluated. The calcitonin gene-related peptide（CGRP） in serum， vasoactive intestinal peptide（VIP） in colon homogenates were evaluated by radioimmunoassay．Immunohistochemical SABC method to observe expression level of SP of colonic specimens. RESULTS Compared with the normal control group，AWR score increased（P<0.01）， The content of serum CGRP， VIP levels in colonic homogenate and expression level of SP in colon decreased markedly in the model group（P<0.01）. After administration with Changkang Granules， the AWR scores of the IBS-D rats were reduced（P<0.01）. The content of serum CGRP， colon VIP level and expression of SP in colon was increased significantly（P<0.05～0.01）. CONCLUSION The therapeutic effect of Changkang Granules on IBS-D rat is obvious． The mechanism could be related to inhibition against the excessive decrease of serum CGRP， colon VIP and expression level of SP in colon in IBS-D rats．