Objective The purpose of this study was to provide a more effective method for the research of prevention and treatment of Graves’ disease by comparing the effects of two plasmid vectors expressing the human thyroid stimulating hormone receptor (TSHR) A subunit gene in inducing animal model of Graves" disease via electroporation. Methods pcDNA3.1-THSR A and pTriEx1.1-THSR A expressing TSHR A subunit were constructed and used to induce Graves" disease by intramuscularly injecting with immediate electroporation once every 3 weeks for a total of 4 times. Mice in thecontrol group were injected with PBS. One week post-second electroporation, blood was gained to measure serum thyrotropin receptor antibody (TRAb). Three weeks post-last electroporation, echocardiography was performed on mice. Mice were sacrificed 4 weeks after the last electroporation, blood, thyroid, orbital tissues were collected, serum total thyroxine (TT4) was measured, and histological examination was performed. Results The average value of serum TRAb in the pcDNA3.1-TSHR A group (n=15) and the pTriEx1.1-TSHR A group (n=13) was (6.9±2.0) U/L and (7.5±2.2) U/L, respectively. The latter was significantly higher than that in the control group (4.9±0.5) U/L (P＜0.05). The average value of serum TT4 in the pcDNA3.1-TSHR A group and the pTriEx1.1-TSHR A group was (41.4±23.8) ng/ml and (63.2±53.7) ng/ml, respectively, both higher than the control group (20.2±4.0) ng/ml (P<0.01). Still, there was no significant difference between thetwo experimental groups (P=0.152). Thyroid pathology showed thyroid follicular epithelial hyperplasia with T-cell infiltration in themodel group. Echocardiography showed that levels of left ventricle mass in the pTriEx1.1-TSHR A group were higher than that in the control group (P＜0.01) and the pcDNA3.1-TSHR A group (P＜0.05). Orbital pathology showed fibrotic changes in the extraocular muscles of mice in the model groups. Conclusions Both pcDNA3.1 and pTriEx1.1 expressing TSHR A subunit were able to induce Graves" disease in mice by electroporation, and the efficiency of two plasmids expressing TSHR A subunit in inducing hyperthyroidism and Graves’ ophthalmopathy was similar. The efficiency of pTriEx1.1-TSHR A inducing thyrotoxic heart disease is better than pcDNA3.1-TSHR A.