In the present series of investigations we first studied the local effects of exogenous substance P (SP) on the hallmarks of neurogenic inflammation, i.e. vascular permeability and blood flow, in the oral mucosa of the rat. Pretreatment with capsaicin was shown to attenuate the symptoms of neurogenic inflammation; therefore, the distribution of nerve fibers displaying substance P‐like immunoreactivity (SP‐IR) in the mandibular mucosa was also assessed in control rats and in animals pretreated with capsaicin both neonatally and in adulthood using immunohistochemical techniques. The application of SP at a dose of 7.5 nmol resulted in an almost 70% increase of vascular permeability (NS) and the administration of a four‐fold higher dose (30 nmol) produced about 150% increase in Evans blue extravasation compared with control values (p<0.05). A similar increase (ca 146%) in vascular permeability was observed in response to 45 nmol SP solution (p<0.05). While the 7.5 nmol SP‐solution failed to affect blood flow, the 30 nmol SP significantly increased it by ca. 38% (p<0.05). The administration of the 45 nmol SP solution resulted in a similar enhancement of blood flow (43%, p<0.05). Capsaicin pretreatment performed either neonatally or in adulthood has reduced the number of SP‐immunoreactive fibers in the oral mucosa. Our functional results suggest that SP may have a role in the experimentally‐induced neurogenic inflamation of the oral mucosa in the rat. This is also supported by our finding that capsaicin pretreatment, known to decrease the number of SP‐immunoreactive fibers in these tissues, reduced the symptoms of neurogenic inflammation.