Objective The aim of this study was to establish a rat model of irritable bowel syndrome. Methods Thirty healthy adult SD rats (mele:female=1:1) were divided into normal control group, model group, and positive control group (pinaverium bromide tablets 15.0 mg/ kg) for 31 days. Body weight, appetite, defecation, voluntary movement of all the rats were determined. The rates of gastric emptying and small intestinal propulsion rate were measured. The serum 5-HT and plasma SP and VIP or 5-HT, SP, VIP in colon homogenates were assessed by radioimmunoassay. Blood biochemical parameters were measured with an automatic biochemical analyzer. The gastric and intestinal morphology was evaluated by histological examination. Results After modeling, the rat weight and food intake were decreased, ad stool quantity was increased. The voluntary movement and gastric emptying rates were decreased, intestinal propulsion rates were increased, and the contents of SP and VIP in blood were decreased, but increased in the colonic homogenate (P<0.05, P<0.01). After treatment, the food intake was increased and stool quantity was decreased, the rat body weight was significantly increased, the amount of voluntary movement and stool returned near to normal, the 5-HT levels in serum or in colonic homogenate were significantly decreased, but plasma VIP levels were markedly increased, and the SP and VIP contents were significantly decreased in colonic homogenate in the positive control group (P<0.05, P<0.01). Hematology indexes had no obvious changes. The gastric and colonic tissue morphology showed no distinct damages caused by the diverse stimulating factors. Conclusions The stimulation of composite factors can be used to successfully generate the rat model of irritable bowel syndrome, showing similar clinical manifestation of this disease in humans.