Abstract： Objective To investigate the effects of genistein on genioglossus muscle function and nuclear factor erythroid 2 related factor 2(Nrf-2)/antioxidant responsive element(ARE) signaling pathway in rats under chronic intermittent hypoxia(CIH) condition in order to find medication treatment of obstructive sleep apnea/hyponea syndrome.Methods Thirty female Sprague-Dawley(SD) rats (8 weeks old) were randomly(random number table) divided into three groups 1 week after ovariectomy: control group(NC group), CIH group, and CIH+genistein treatment group(T group).Rats in the latter two groups were exposed to CIH for 8 h/d for 5 weeks.Electrophysiological method was used to detect the change of genioglossus muscle function, and real-time reverse transcription(RT)-PCR and Western blotting were used to determine the level of Nrf-2 gene and protein.Results Compared to NC group, the contractive properties of genioglossus muscle fatigue test at every time set was significantly decreased in CIH group(P＜0.05).Compared to CIH group, the contractive properties was significantly increased in T group(P＜0.05).The level of Nrf-2 gene and protein were less in CIH group(0.54±0.11 and 0.35±0.13) than in NC group(1.00±0.00 和 1.00±0.00)(P＜0.05).Compared to CIH group the level of Nrf-2 gene and protein were increased in T group (0.76 ± 0.16 and 0.63 ± 0.14)(P＜0.05), however, it was still less than the level in NC group(P＜0.05).Conclusions CIH attenuates genioglossus muscle fatigue resistance under chronic intermittent hypoxia through Nrf-2/ARE signaling pathway.Genistein protects genioglossus muscle function through up-regulation of the level of Nrf-2 gene and protein.