Objective To observe and compare the effects of sex, antigen dose, injection frequency, and modeling time on a porcine thyroglobulin ( pTg)-induced experimental autoimmune thyroiditis ( EAT) mouse model. Methods A total of 80 SPF CBA/ J mice were selected to establish an EAT model under various conditions: sex ( 60 females and 20 males), antigen dose (pTg 50 μg, 100 μg, and 200 μg), and injection frequency and modeling duration (two injections in 28 days, three injections in 28 days, or three injections in 35 days). The effects of the different modeling strategies were compared using thyroid pathology scores, serum TgAb titers, serum TT4 levels, proportions of Treg and Th17 cells in the spleen, and the levels of related transcription factors. Results (1)Under the same modeling conditions, the degree of thyroid lymphocyte infiltration and EAT scores were lower, and the TgAb titers, proportion of Th17 cells, and IL-17A expression levels were significantly lower, in male mice than female mice. (2) TgAb titers, TT4 levels, proportion of Th17 cells, and expression levels of RORγt and IL-17A in the 50 μg model group were significantly lower than those in the 100 μg model group, and the expression level of Foxp3 in the 200 μg model group was significantly higher than that in the 100 μg model group. ( 3) EAT scores, TgAb titers, TT4 levels, proportion of Th17 cells, and expression levels of RORγt and IL-17A were significantly increased, and the proportion of Treg cells was significantly decreased, in the three injections in 28 days group. Conclusions Selecting female CBA/ J mice, increasing the antigen dose, increasing the modeling frequency and reducing the modeling time improved the EAT modeling effect.