Objective: To preliminarily investigate the mechanism of action of metformin in the treatment of Hashimoto′s thyroiditis. Methods: Forty-five healthy SD female rats were randomly divided into control group, model group and metformin-treated group, and the rats were simulated with a model of Hashimoto′s thyroiditis by immuno-injection of high iodine water combined with thyroglobulin and Freund′s adjuvant. After successful modeling, the control group and the model group were perfused with saline, and the metformin group was administered with 300 mg/kg metformin by gavage for 4 weeks, and the rats in each group were executed and sampled. Serum thyroid function indexes(TSH, T3, T4, TGAb, TPOAb) and thyroid tissue inflammatory factors(TNF-α, IL-10, IL-6,IL-12) levels were measured by ELISA; thyroid tissue pathological changes were observed by HE staining; thyroid tissue apoptosis was detected by TUNEL fluorescence staining; thyroid tissue expression of Fas, Fas-L was detected by immunohistochemistry; the expression of Fas, Fas-L, FADD and cleaved caspase-3 in thyroid tissue was determined by Western blot; Fas, Fas-L and FADD mRNA expression in thyroid tissue was detected by qRT-PCR. Results: Compared with the control group, serum levels of TSH, TGAb, TPOAb, positive cell ratio, levels of TNF-α, IL-6 and expression of Fas, Fas-L, FADD and cleaved caspase-3 in thyroid tissue were significantly higher in the model group, and serum FT3 and FT4 levels and IL-10 and IL-12 levels in thyroid tissue significantly decreased(P<0.01). Compared with the model group, serum levels of TSH, TGAb, TPOAb, positive cell ratio, TNF-αand IL-6 contents and expression of Fas, Fas-L, FADD and cleaved caspase-3 in thyroid tissue were significantly lower in the metformin group, and serum FT3 and FT4 levels and IL-10 and IL-12 contents in thyroid tissue were significantly higher(P<0.05). Conclusion Metformin inhibits the progression of Hashimoto′s thyroiditis, and its mechanism of action may be related to the inhibition of the Fas/Fas-L-mediated apoptotic pathway.