The oral care has been focused on as one of the method of prevention from bedridden situation and rehabilitation in the elderly persons. Although some previous reports have demonstrated the association of the cerebral activation with oral care including intra-oral cold stimulus, the effect of intra-oral cold stimulus on the prefrontal cerebral cortex activation has remained uncertain. In the present study, we examined the effect of intra-oral cold stimulus on the cerebral prefrontal cortex activation using near-infrared spectrography in 11 male young adult subjects (aged 20-47 years, mean age 28.1 ± 9.6 years). Intra-oral cold stimulus using crushed ice for 60sec significantly increased blood flow levels in bilateral prefrontal cortex (PFC), compared to the control condition. In addition, the increase in PFC blood flow with intra-oral cold stimulus remarked in bilateral visceral lateral region of PFC (VL-PFC) and orbitofrontal region (OFC) corresponded to the activated regions after learning task such as simple calculation. However, the increase of blood flow in these PFC regions with cold stimulus on bilateral palms of the hand or soles of foot showed lower level compared to those with learning task as positive control. These findings suggest that the intra-oral cold stimulus as an oral care may lead to an increase in blood flow in PFC and may indicate that the intra-oral cold stimulation may be applied as a useful method for enhanced neurocognitive function in the elderly rehabilitation program and the prevention from bedridden situation via the neuronal activities in PFC.