Olfactory dysfunction is an early symptom of Alzheimer’s disease (AD). The olfactory bulb and neocortex receive cholinergic basal forebrain inputs which degenerate in AD patients. Nicotinic acetylcholine receptors (nAChRs) in the brain play a crucial role in vasodilation in the neocortex induced by basal forebrain cholinergic activation or nicotine injection. Information about the sense of smell is conveyed by the olfactory nerve, or by the intranasal trigeminal nerve when irritating odors. We recently reported that nicotine potentiates the olfactory bulb vasodilation induced by olfactory nerve stimulation. This study aimed to clarify the effect of trigeminal olfactory stimulation on cerebral blood flow and role of nicotinic cholinergic transmission.Using anesthetized rats, regional blood flow in the olfactory bulb and frontal cortex was measured with laser Doppler flowmetry or laser Speckle contrast imaging. Arterial blood pressure was simultaneously recorded. Intranasal trigeminal nerve was stimulated electrically.In central nervous system-intact condition, intranasal trigeminal nerve stimulation produced increases in blood flow of both olfactory bulb and frontal cortex with pressor response. In rats spinalized at the upper thoracic level, the intranasal stimulation did not elevate blood pressure and olfactory bulb blood flow, but still increased blood flow in the frontal cortex. Intravenous injection of nicotine (30 mg/kg) did not influence the olfactory bulb, but potentiated the response in the frontal cortex.It is suggested that sensory processing of irritant odors via the trigeminal nerve involves the neocortex rather than the olfactory bulb, and activation of nicotinic cholinergic transmission enhances those processing.