Background: To determine the topical effect of intravesical capsaicin on bladder mucosa in graded doses. Methods: Intravesical reagent was instilled in four groups of age and weight matched female rats: 2, 4 and 40 mM capsaicin and saline. Intravesical capsaicin was dissolved in 30% ethanol (EtOH) and saline. The animals (n = 4 each group) were sacrificed at the 13th day after a total of 5 instillations at days 0, 2, 5, 7 and 10. Whole bladders were harvested, fixed in 10% buffered formalin, and paraffin embedded. Tissue blocks were blind coded and sectioned (5-mm thickness) for histopathological analysis. All sections were stained with hematoxylin and eosin and examined under light microscopy. Fishers' exact test was used for statistical analyze. Results: The rats in intravesical capsaicin groups (2, 4, and 40 mM) exhibited similar bladder mucosal histology. Instillation of saline demonstrated no effect on bladder histology, whereas instillation of intravesical capsaicin induced acute thinning effect of the epithelium, submucosal edema, vascular ectasia and congestion and also eosinophil infiltration, that was statistically insignificant, in some parts of the stroma of only one bladder (25%) in the 40 mM group. Conclusions: All bladders in intravesical capsaicin groups demonstrated a histologically similar mucosa, except for the eosinophil infiltration in some parts of the stroma of a bladder in 40 mM group and which was statistically insignificant. Thus, we conclude that, in the resistant cases treated with intravesical capsaicin, concentrations may be risen up above the widely used doses, if an adequate anesthesia is maintained.