Mouse strain differences exist in post-hypoxic ventilatory behavior, specifically, the C57BL/6 J (B6) mouse exhibits irregular breathing including apnea during re-oxygenation after acute hypoxic exposure, while A/J mouse does not. This phenomenon of the B6 mouse responding to the hypoxia-reoxygenation cycle which is a mimic of human sleep apnea syndrome let us consider the B6 mouse as an animal model of sleep apnea. Moreover, the B6 mouse tends to show spontaneous apnea and post-sigh apnea compared to the A/J mouse. In this brief review, we present evidence that pharmacologic approaches as well as genetic modification can improve irregular breathing including apnea in the B6, suggesting that these pharmacologic treatment might be effective for the patients with sleep apnea who cannot tolerate nCPAP. Moreover our findings regarding genetic difference and modification should be helpful to explore the pathogenesis of sleep apnea.