This study investigated a putative contribution of mast cells and C-sensory fibers to differences in the development of inflammatory edema following the injection of concanavalin A (Con A) into the hind paws of Dark Agouti (DA) and Albino Oxford (AO) rats. The treatment of adult rats with mast cell-depletor compound 48/80 and neonatal depletion of C-sensory fibers independently revealed that leukocyte composition of the inflamed paws and lymph nodes during local inflammatory response to Con A was generally regulated in a similar way in DA and AO rat strains. However, in DA and AO rats, the decrease and the increase of Con A-induced plasma extravasation were associated with mast cell depletion and activation, respectively, whereas neonatal capsaicin treatment activated dermal mast cells and potentiated inflammatory plasma extravasation only in adult rats of DA strain. Hence, strain differences in the development of the inflammatory response to Con A are probably controlled by the differences in the interplay between mast cells and C-sensory fibers in DA and AO rats.