Objective To explore the biological indicator of diagnosis and treatment of irritable bowel syndrome (IBS), to explore the mechanism of action of Wuji Pill on Irritable Bowel Syndrome (IBS). Methods (1) Post Inflammatory Irritable Bowel Syndrome (PI-IBS) animal model was established by acetic acid plus restraint stress method. (2) The colonic motor ability of rats was evaluated by colon motility index (MI), the number of fecal particles discharged within 2 h, and the time of glass pellet discharged. (3) The formation of PI-IBS model rats and the therapeutic effect of WJW was observed. (4) The levels of calcitonin gene-related peptide (CGRP), motilin (MTL), neuropeptide Y (NPY), substance P (SP), somatostatin (SS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) in the brain and colon tissues of PI-IBS rats were measured by ELISA. Results (1) successfully established the rat PI-IBS model. Compared with the normal group, the weight of the model rats decreased; the food intake decreased; the amount of defecation increased; loose stools and amorphous soft stools appeared; autonomic exercise decreased; colon MI increased significantly (P <0.05); the number of fecal particles discharged increased significantly (P <0.05); the glass pellet discharge time was significantly shortened (P <0.05). (2) WJW treatment 7d can significantly improve a variety of symptoms. Compared with the normal control, the levels of CGRP, SS and VIP in the brain tissue of PI-IBS rats were significantly increased (P <0.05), and the NPY concentration was significantly decreased (P <0.05). However, the treatment of WJW can significantly reduce CGRP, SS and VIP levels (P<0.05); and significantly increased the NPY concentration level (P<0.05). (3) Compared with the normal control, the level of CCK, NPY, MTL, SS and VIP in colonic tissue of PI-IBS rats were significantly decreased (P<0.05), while WJW can significantly increase CCK and VIP levels. Conclusion WJW can treat IBS by regulating the levels of various brain-gut peptides in the brain and colon tissue of IBS rats. These adjustable and anomalous brain-gut peptide may be a potential biomarker for the diagnosis and treatment of IBS.