Objective To investigate the expression changes of islet amyloid polypeptiole(IAPP) and glucose transporter 2(GLUT2) in islet β cells during heroin withdrawal induced by naloxone, methadone detoxification treatment, and heroin relapse. Methods Male SD rats (n=32) were randomly divided into a normal control group (NCG, n=8) and an experiment group (EG, n=24). The EG was further divided into heroin withdrawal group (HWG), methadone detoxication group (MDG), and heroin relapse group (HRG). Pancreas was drawn from each group. Immunohistochemistry and image analysis were used to detect the expression of IAPP and GLUT2. Results As compared with the normal control, the immunostainning of IAPP and GLUT2 was stronger in β cells of islets from heroin withdrawal and relapse rats than that in controls; the numerical density on area of IAPP also increased; the mean gray values decreased in these two groups. No difference was found in the immunostainning, the mean gray values and the numerical density on area during detoxification treatment compared to controls. Conclusion During heroin withdrawal and relapse, the synthesis of IAPP and GLUT2 increased, while they became decreased in methadone detoxification. The changes of IAPP and GLUT2 were consistent and had same rhythm in three stages. IAPP and GLUT2 took part in energy metabolic process, which may be related to food intake and body weight, or protective function toβcells.