Objective To study the changes of 5-hydroxytryptamine(5-HT)，its receptor, IL2 and IL-6 in rats’ ileum with spleen deficiency combined with gastric ulcer. To explore the pathogenesis of this disease and the therapic mechanism of sijunzi decoction. Methods Immunohistochemical technique, image analysis, radioimmunoassay and Western blotting were used. Results The 5-HT-positive cells of rat ileum were detected in mucosal and glandular cells.The 5-HTR-positive cells of rat ileum were found in the connective tissues between the intestinal villus and intestinal glands, and in neuroplex and smooth muscle tissues. The expression of 5HT and 5-HTR in ileum increased during the experimental spleen deficiency combined with gastric ulcer in rats. The 5-HTR level of rat ileum was higher. After treatment with Sijunzi decoction, all the changes have been reversed. The level of IL-2 and IL-6 increased during the early period of this disease. When the disease doveloped, the synthesis or secretion of IL-2 and IL-6 decreased. Conclusion The increased contents of 5-HT and its receptor in ileum tissues might be one of the causes of spleen-deficiency combined with gastric ulcer in rats. The mechanism of Sijunzi decoction is to reverse the changes. And the changed activity of IL-2 and IL-6 may be related with the degree of