Objective: The endothelial or epithelial tight junctions (TJs) create a barrier to diffusion of solutes. It is suggested that the structure and function of the blood-brain barrier (BBB) have been damaged on the study of the experimental diabetic models. There are experimental evidences that the expression of the TJ proteins—-occludin, zonula occludens-1 (ZO-1) and claudin-5 in the blood-brain barrier has been changed in experimental diabetic rats, leading to changes in the function of the BBB. In recent years, scholars have found that the epithelial membrane protein 1 (EMP1), colocalizing with the TJ proteins, is a novel TJ-associated molecule at the BBB. In this study, an experimental diabetic model in rats was established successfully and the expression of EMP1 in the BBB was examined at the different time points.Methods: Healthy adult male Sprague-Dawley rats were randomly divided into 2 groups: Streptozotocin (STZ) induced diabetic group (STZ group) and the control group (CON group). After the model was established successfully, each group was divided into 3 subgroups: 2 weeks, 4 weeks, 8 weeks. At the corresponding time point, the body weight and the blood glucose of rats in each group were both measured. After the perfusion with the 4% paraformaldehyde solution, the rats were sacrificed. The brains were embedded in paraffin and the expression of EMP1 was detected by immunohistochemistry.Results:1. The level of blood glucose of STZ rats in each subgroup comparing to that of the CON rats in the corresponding subgroup was significantly increased. The level of blood glucose of STZ rats in 4 week group and the 8 week group was also significantly increased comparing to that of 2 week group.2. The expression of EMP1 in STZ rats and CON rats was not significantly different in 2 week group and 8 week group.3. The expression of EMP1 in STZ rats was significantly increased in 4 week group.4. The expression of EMP1 in STZ rats showed no significant difference among any subgroup, and the expression of EMP1 in CON rats also showed no significant difference among any subgroup.Conclusion: The expression of EMP1 in the blood-brain barrier of the frontal cortex on the experimental diabetic rats was changed. The expression of EMP1 was significantly increased at 4 weeks after the experimental diabetic model was successfully established.