Recombinant human epidermal growth factor (rhEGF) has potential benefit for the mucositis induced by radiation therapy as a therapeutic setting. In this study, we aimed to investigate the effects of rhEGF treatment on the radiation-induced changes in epithelial transport function, before the occurrence of the definitive histological mucosal changes. C3H/He mice received 0, 4, or 8 Gy irradiation and/or EGF treatment (rhEGF 0, 1 and 5mg/kg, i.p., 5 days). At day 7, we recorded short circuit current (Isc) of the upper tracheal epithelium using the flow-type Ussing chamber method, with histological analysis. As a result, there was no evident pathological change in the epithelium from the irradiated and/or rhEGF treated mice at day 7. The initial level of Isc and amiloride-sensitive Isc (ΔIsc,Amil) were decreased after 8 Gy irradiation, reflecting suppression of basal Na+ absorption. The decreased ΔIsc,Amil was recovered by rhEGF treatment. In conclusion, epithelial Na+ channel-dependent basal Na+ absorption was primarily affected by irradiation, before the pathological changes. The recovery of basal Na+ absorption (ΔIsc,Amil) suggested a potentially beneficial effect of early rhEGF treatment for irradiation-induced suppression of the upper aerodigestive epithelial functions.