OBJECTIVE: To study the prophylactic effects of nasal tolerance with a dual analogue, Lys262-Ala207, on the mouse model of experimental autoimmune myasthenia gravis (EAMG) and the underlying mechanism. METHODS: Mouse model of EAMG was induced by intraperitoneal injection of mAb35. Lys262-Ala207 or PBS was given nasally before 10 days (study group A and control group A) or on the day (study group B and control group B) of immunization for 10 days. Clinical syndromes were evaluated after immunization. Serum level of acetylcholine receptor antibody (AChR-Ab) IgG was detected using ELISA. The number of monouclear cells expressing CD4+ and CD4+ CD25+T from spleen was measured using flow cytometry. RESULTS: Compared with the corresponding control groups, the clinical syndromes were improved (P<0.01) in mice from the study groups A and B. The positive rate of the repetitive nerve stimulation (RNS) test in the study groups A and B was significantly lower than that in the corresponding control groups (P<0.01). The study group A showed lower positive rate of RNS than the study group B (P<0.05). The serum levels of AChR-Ab IgG in the study groups A and B (15.01±1.09 and 19.23±1.31 μg/mL) decreased compared with that in the corresponding control groups (28.12±1.28 and 29.35±1.28 μg/mL) (P<0.01). The study group A mice had lower serum AChR-Ab IgG levels than the study group B (P<0.01). The number of CD4+ CD25+T cells in the study groups A (4.516±0.598%) and B (3.671±0.300%) increased significantly compared with that in the corresponding control groups (2.661±0.411% and 2.412±0.500%) (P<0.01) and more CD4+ CD25+T cells were found in the study group A than in the study group B (P<0.01). CONCLUSIONS: Nasal administration with dual analogues may ameliorate clinical syndromes in EAMG rats, which may be associated with decreased serum AChR-Ab IgG levels and increased number of CD4+ CD25+T cells from spleen.