Objective: To prepare and evaluate an animal model of autoimmune thyroiditis with depression based on the NLRP3/Caspase-1/GSDMD pathway. Methods: 32 NOD.H-2H4 mices were randomly divided into normal group (N group), depression group (DP group), autoimmune thyroiditis with depression group (AIT+DP group), autoimmune thyroiditis group ( AIT group), 8 animals in each group. The N group was fed normally, the DP group was subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, the AIT group was given 0.05% sodium iodide water to establish an autoimmune thyroiditis model, and the AIT+DP group was subjected to 5 weeks of chronic unpredictable mild stress (CUMS) on the basis of establishing the AIT animal model. 5 weeks of CUMS to establish the AIT+DP animal model. Evaluate whether the mouse autoimmune thyroiditis model has been successfully prepared by observing the thyroid tissue structure and lymphocyte infiltration of mice and serum TGAb and TPOAb levels; by measuring body weight, sugar water preference rate, open field behavior (central quadrant time, central quadrant time Proportion, number of standing, frequency of defecation, hair grooming time), and hippocampal pathological changes were used to evaluate the depression status of mice. If the model mice meet the above-mentioned indicators related to depression and autoimmune thyroiditis, it indicates that the AIT+DP animal model has been successfully prepared. Results: Compared with the N group, the serum TGAb and TPOAb levels in the AIT group and the AIT+DP group were significantly increased (P<0.01). A large number of inflammatory cells were infiltrated in the thyroid gland. The central quadrant time and central quadrant time of the mice in the DP group and the AIT+DP group Proportions, times of standing, frequency of defecation, and hair grooming time were reduced to varying degrees, glial cells in the cerebral cortex increased, neuronal cells decreased, accompanied by some nuclear atrophy, and the expression levels of NLRP3, IL-1β, Caspase-1, and GSDMD-N Significantly increased, especially in the AIT+DP group (P<0.01). Conclusion: 0.05% sodium iodide water and CUMS can better simulate the external performance and internal index changes of AIT+DP model animals, and can provide an animal model reference for research on AIT+DP disease.