Objective To observe the effect of heroin on EGF and IL-2 positive cells in the submandibular gland of rats. Methods Normal SD rats were divided into normal control group (NGC),saline control group (SCG)and heroin dependence group (HDG). The heroin dependent model of rats was established by subcutaneous injection of heroin, and submandibular glands were excised on the following days respectively: the 10th, 17th, 24th, 31th and 38th. Immunohistochemical SABC method, image analysis and cells calculation were used in the study. BR> Results 1. As compared with those of the NCG, the number of EGF and IL-2 positive cells and the intensity of staining in SCG didn’t change obviously. 2. During heroin dependence, the immunohistochemical staining showed that the number of EGF and IL-2 positive cells increased obviously(P<0.05); meanwhile, the results of image analysis showed that the mean grey degree of EGF and IL-2 positive cells were lower than that of NCG and SCG groups. 3.The colocalization of EGF and IL-2 was proved in the submandibular gland of rats.Conclusion The number of EGF and IL-2 positive cells and the intensity of staining change regularly in the submandibular gland of rats. It suggestes that the EGF and IL-2 from submandibular gland of rat were involved in the regulating proc