Objective  To investigate the relationship between the expression of Wnt signaling pathway, autoimmune regulator (AIRE) and type 1 diabetes (T1D) tissue specific antigen (TSAs) insulin 2(Ins2) and glutamic acid decarboxybase(GAD67) in thymus and the occurrence of T1D in NOD/Ltj mice with spontaneous type 1 diabetes (T1D).   Methods  Sixty female NOD/Ltj mice were divided into three groups: 3 weeks group, 16 weeks non-onset group and 16 weeks onset group. Two consecutive non-fasting blood glucose levels ≥ 11.1 mmol/L were considered as the occurrence of T1D. Pancreatic HE staining was used to observe the occurrence of islet inflammation. Anti-Ins and CD45 immunohistochemical staining showed islet β cells or infiltrating inflammatory cells. The protein levels and mRNA expressions of Wnt7a, β-catenin, AIRE, Ins and GAD67 in thymus were detected by Western blotting and Real-time PCR. The proportion of T cells in thymus was analyzed by flow cytometry.    Results  1. With the occurrence of T1D, the islet structure was destroyed, a large number of lymphocytes infiltrated, and the remaining islet cells were reduced. A large number of CD45+ cells were observed around Ins+ islet β cells. 2. The protein levels and mRNA expressions of Wnt7a, β-catenin, AIRE, Ins2 and GAD67 in thymus decreased with age. The expression of Ins in thymus decreased in the same week-old group compared with that in the control group. 3. Compared with the 3 weeks group, the proportion of CD4 and CD8 single positive T cells in the 16 weeks group was lower; In the 16 weeks group, the proportion of CD4 and CD8 single positive T cells increased, while the proportion of CD4 and CD8 double positive T cells decreased.   Conclusion  Wnt7a/β-catenin signaling pathway may be involved in the occurrence and development of T1D by regulating AIRE expression and down-regulating T1D-related TSAs expression.