Objective The plasma concentrations of 10 active components in Wuji Wan were measured at various time points after single and multiple oral administrations to compare its pharmacokinetic characteristics in normal rats and rats with chronic visceral hypersensitivity irritable bowel syndrome (CVH-IBS) in different courses. Methods The CVH- IBS rat model was established by the neonatal rat colon balloon stimulation method and visceral sensitivity was evaluated. After single or multiple intragastric administrations of Wuji Wan, blood was collected from the jugular vein at various time points. Ultra-performance liquid chromatography-MS / MS was used to simultaneously measure the plasma concentrations of 10 active components of Wuji Wan in plasma and compare differences in pharmacokinetic parameters. Results Visceral sensitivity was enhanced in CVH-IBS rats. Compared with a single dose, the peak time (t_max) of multiple doses in normal and model rats was earlier. The difference between model and normal rats after a single dose verified the previous experimental results. Compared with normal rats, the active component C_max, AUC_0-t and Cl of Wuji Wan in model rats were changed significantly after multiple administrations. The C_max of berberine hydrochloride, coptisine hydrochloride and epiberberine was increased significantly, while that of palmatine hydrochloride, jatrorrhizine hydrochloride, dihydroberberine, evodiamine and evodia lactone was decreased significantly. Epiberberine C_max was decreased significantly. Coptisine hydrochloride and epiberberine AUC_0-t was increased significantly. Palmatine hydrochloride, dihydroberberine, jatrorrhizine hydrochloride, evodiamine and evodia lactone AUC_0-t was decreased significantly. Coptisine hydrochloride and evodia lactone Cl was increased significantly. Epiberberine Cl was reduced significantly. Palmatine hydrochloride and albiflorin t_{1/ 2} was reduced significantly. Jatrorrhizine hydrochloride V_d was increased significantly. By comparing multiple and single administrations in model rats, the C_max of active components coptidis berberine hydrochloride, jatrorrhizine hydrochloride, epiberberine and dihydroberberine was decreased significantly and the C_max of jatrorrhizine hydrochloride was decreased significantly. The t_{1/ 2} and Cl of paeoniflorin, the active component of Radix Paeoniae Alba, were significantly decreased and increased, respectively. Conclusions There are significant differences in the pharmacokinetic behaviors of the active components in Wuji Wan in normal, CVH-IBS and CVH-IBS rats at the late stage of treatment with Wuji Wan. This may be related to the disruption of the intestinal barrier in the early stage of IBS treatment, repair of the intestinal barrier in the late stage of treatment, accumulation of drugs in hepatic and enteric circulation, the activity of liver enzymes, and other metabolic changes.