Objective To explore the morphological changes of 5-HT, Somatostatin（SS）, Substance P（SP） immunoreactive(IR) cells in rat rectum during heroin dependence period. Methods Normal SD rats were divided into normal control group (NCG), saline control group(SCG),and heroin dependence group(HDG).To make the heroin dependence model of rats by subcutaneous injection of herion, and excise the rectum. Immunohistochemical SABC method, counting the number of cells and image analysis were used in the study. Results Compare with the NCG and SCG, All the number and immunohistochemical reaction of 5-HT, SS, SPIR cells increased(EM>P/EM><0.05) in rectum during heroin dependence. The result of image analysis showed that the mean of grey degree of the rectum 5-HT, SS, SPIR cells decreased in HCG as compared with the NCG and SCG(EM>P/EM><0.05).And in 5-HT, SS-IR cells, the mean grey scale were the lowest on 31st day(EM>P/EM><0.05). But in SP-IR cells, the mean grey scale was the lowest on 38th day(P<0.01). Conclusion The changes manifested that the function of 5-HT, SS and SP-IR ce