The skeletal muscle specific chloride ion channel (ClC-1) plays an important role in regulating neuromuscular transmission and muscle fiber excitability during activity. Recently, ClC-1 channel inhibition was shown to improve muscle function in generalized myasthenia gravis (MG). The study included both preclinical animal models and patients with MG and showed that improvement in muscle function and performance in the rat model of MG translated to improvement in symptoms of patients with MG following administration of a ClC-1 inhibitor. Here, we examined the effect of ClC-1 inhibition in muscle-specific kinase (MuSK) MG; a rare and frequently more severe subtype of MG with an acute onset affecting mainly the facial-bulbar muscles and frequent occurrences of respiratory crises. A blinded study of a rat model of MuSK MG was used, wherein rats were immunised with a MuSK specific antigen. Hereafter the rats were stratified into groups before treatment with either vehicle or a ClC-1 inhibitor dosed orally once daily for 14-days. To evaluate the effect of treatment, neuromuscular transmission by stimulated EMG, muscle function by gait analysis, and pulmonary function by unrestrained whole-body plethysmograph were measured. Overall, the study showed that inhibition of ClC-1 with an orally bioavailable small molecule had a positive effect on EMG, muscle, and lung function in a rat model of MuSK MG. Additionally, higher body weight and increased survival were also observed in the ClC-1 treated group relative to vehicle. In summary, administration of a ClC-1 chloride channel inhibitor improved disease symptoms and survival in a rat model of MuSK myasthenia gravis.