Objective To explore the effect of metformin on thyroid hormone in rats with hypothyroidism and its mechanisms. Methods A total of 36 three-month-old male SD rats were randomly divided into normal control (NC) group and hypothyroidism (HT) group, metformin (Met) group. The rats in HT group and Met group was fed with 0.01% amino three triazole (AMT) water for 4 weeks to create hypothyroidism rat model, while NC group were fed with normal water. After modeling, the rats in Met group were intragastrically administrated with metformin 200 mg/kg, while the rats in HT group and NC group were intragastrically administrated with equal volume of 0.05% carboxymethylcellulose sodium (CMC-Na). After intragastric administration for eight weeks, the rats in each group were sacrificed to observe thyroid tissues with H-E staining, and to detect prothyrotropin-releasing hormone (proTRH) mRNA expression with qPCR assay. After intragastric administration for 8 and 12 weeks, serum T3 and T4 levels were detected using electrochemiluminescence assay, rat thyroid sodium/iodide symporter (NIS) mRNA and protein expressions were detected by qPCR and Western blotting, respectively. Results T3 and T4 levels of rats in HT group were significantly lower than those in NC group after 8 and 12 weeks of intragastric administration, while T3 and T4 in Met group were significantly higher than those in HT group (P<0.05). At week eight of intragastric administration, H-E staining showed that there was a greater variability in the size of folliculars, in which a large number of colloid and vacuoles were observed in the NC group; thyroid folliculars in the HT group were shrunk, the follicular epithelial tissues were columnar, and vacuoles around the follicles were decreased; and the thyroid follicular epithelial tissues hyperplasia in the Met group was slightly improved versus the HT group. At week eight of intragastric administration, the results of qPCR showed that thyroid tissue NIS mRNA and hypothalamic proTRH mRNA expressions in HT group were higher than those in NC group, while those in Met group were lower than those in HT group (P<0.05); Western blotting results showed that NIS protein expression in Met group was significantly lower than that in HT group (P<0.05), and there was no significant difference in NIS protein expression between HT group and NC group (P>0.05). After 12 weeks, there was no significant difference in NIS mRNA expression between HT group and Met group (P>0.05), while NIS protein in Met group was significantly higher than that in HT group (P<0.05). Conclusion Metformin can increase the thyroid hormone level, but its short-term mechanism may not be related to promoting the level of NIS.