Objective: To investigate the therapeutic effect of Fuan decoction on postoperative ileus (POI) and its related mechanisms. Methods: Ninety mice were randomized into sham operated control group, POI model group and Fuan decoction pretreatment group, and then the rats underwent the conventional procedure of POI establishment or sham operation, respectively. The content of tryptase and histamine of the small intestinal tissue was detected by ELISA method. The number of mesenteric mast cells was counted and their degranulation was observed under light microscope after toluidine blue staining. The myeloperoxidase (MPO) activity of the small intestinal tissue was determined by colorimetric method and the carbon powder moving rate was also measured. Results: The content of tryptase and histamine, and the MPO activity of the POI model group were all increased significantly compared with those of the sham operated control group (all P<0.01), but the elevations of these parameters were remarkably inhibited in the Fuan decoction pretreatment group and these had statistical differences compared with the POI model group (all P<0.01). No significant difference in the number of mast cells was found among the groups, but the degranulation of mesenteric mast cells was evident in POI model group and was inhibited in Fuan decoction pretreatment group. The carbon powder moving rate was significantly decreased in POI model group after surgery (P<0.01), which was significantly higher in Fuan decoction pretreatment group than that of the POI model group (P<0.01). Conclusion: Fuan decoction can reduce the production of intestinal tryptase and histamine after surgery and inhibit the degranulation of mast cells and their inducttion of inflammatory response, and thus it has the effect of preventing and alleviating postoperative Ileus.