Purpose This study is intended to explore the effect of chronic electrical stimulus at a lower physiological frequency on expression of myosin heavy chain (MHC) isoforms mRNA and sarcoplasmic reticulum-ATPase (SERCA) activity in genioglossus of rabbits with chronic hypoxia.Methods Twenty-four adult rabbits were randomized into control group (A), chronic hypoxia group (B), 2.5 Hz electrical stimulus group (C) and (2.5+40)Hz electrical stimulus group (D).After the rabbits had been fed with free access to food and water in a hypoxia cabin 10 h a day for 4 weeks, those in groups C and D received electrical stimulus on genioglossus at a frequency of 2.5 Hz and (2.5+40)Hz, respectively.However, the rabbits in group B received no electrical stimulus.Exprseeion of MHC isoforms mRNA in genioglossus of rabbits in 4 groups was determined by RT-PCR and SERCA activity was assayed by determination of inorganic phosphate.Results Expression level of MHC-Ⅰ mRNA in genioglossus muscle in chronic hypoxia group was significantly lower (P<0.05) and that of MHC-Ⅱ a mRNA was markedly higher (P<0.05) than that in the control group.Meanwhile, SERCA activity of genioglossus muscle was significantly lower in chronic hypoxia group than in the control group (P<0.05).Expression levels of MHC-Ⅰ mRNA and MHC-Ⅱ a mRNA in genioglossus muscle were up-regulated significantly (P<0.05) while those of MHC-Ⅱ b mRNA, especially in the (2.5+40)Hz electrical stimulus group, were significantly down-regulated (P<0.05) than those in the chronic hypoxia group after finishing stimulation.Electrical stimulation rose SERCA activity of genioglossus muscles in rabbits with hypoxia, especially in (2.5+40)Hz electrical stimulus group (P< 0.05).Conclusion Lower physiological frequency chronic electrical stimulation at a frequency of (2.5+40)Hz might reduce possibility of collapsing of upper airway by reconstructing muscle fiber isoforms of genioglossus and making adaptable changes in contractile properties and fatigue-resistance.Based on the results, we suggest that lower physiological frequency chronic electrical stimulation may be a new treatment for OSAHS.