EtOH has the devastating effect on traumatic brain injury (TBI). It is known that EtOH decreased survival rate to approximately 50% by brain edema augmentation 24 hr after TBI (Katada et al, 2009. J Neurotrauma). Brain aquaporin-4 (AQP4), an water channel, could be involved to brain edema augmentation after TBI under EtOH consumption (Katada et al, 2012. Am. J Pathol). We also reported that sodium ion concentration in blood was decreased after TBI in rat. AQP4 is regulated by or co-expressed with Na-K ATPase, Na(+)-K(+)-2Cl(-) co-transporter. EtOH is also involved in those channels. From these findings, we hypothesized that sodium channel may affect AQP4 expression under EtOH. In this study, rat primary astrocytes were obtained from Wistar/ST rat pup brain. They were incubated in iso-sodium MEM (NaCl: 680 mg/dL) and hypo-sodium (NaCl: 410 mg/dL) or hyper-sodium MEM medium (NaCl: 950 mg/dL) for 30 min, 3 hr, 6 hr, 24 hr. EtOH was added to each medium simultaneously. And they were incubated in EtOH with tetrodotoxin (TTX) for 1 or 3 hr. After exposure, AQP4 protein expression was checked by western blotting and mRNA was checked by RT-PCR. AQP4 expression was increased in 3 hr hypo-sodium medium exposure. Hypo-sodium with EtOH did not change AQP4 expression significantly, on the other hand, hyper-sodium with EtOH decreased AQP4 expression for short time exposure, and increased it for long time exposure. Hyper-sodium increased astrocyte AQP4 expression under EtOH exposure. TTX changed astrocyte AQP4 expression. These findings suggest that astrocyte AQP4 expression is regulated by sodium ion or its channel under EtOH exposure.