Objective: The aim of the study was to investigate the role of montelukast (ML), acysteinyl leukotriene-1 receptor antagonist, on the water avoidance stress (WAS) –induced degeneration of the rat urinary bladder mucosa.Methods: In WAS group, rats were exposed to WAS two hours daily for five days.In WAS+ML group, rats were administered ML (10 mg/kg; i.p.;) following every WASexposure for 5 days. In control group, rats were injected vehicle solution only. Theurinary bladder was evaluated for general morphology at light microscope. Mastcell activation and uroplakin distribution were assassed with immunohistochemistry.Glycosaminoglycan (GAG) distribution and urothelial permeability were observedusing ruthenium red (RR) staining techniques in transmission electron microscopeand luminal urothelial cells were observed with scanning electron microscope. Tissuemalondialdehyde (MDA) and gluthatione (GSH) levels were also analysed.Results: Irregular GAG layer and uroplakin distribution, penetration of RR inthe intercellular spaces and dilated tight junctions in urothelial layer, increase ininflammatory cell infiltration, in number of both granulated and activated mast cells,and were observed in the WAS group. The MDA level was increased, and GSH levelwas decreased significantly in urinary bladder in the WAS group in comparison withthe control group. Quite regular GAG layer, uroplakin distribution and tight junctionsin most regions, decrease in inflammatory cell infiltration and both of activated andgranulated mast cells in the mucosa, were observed in WAS+ML group. Moreover,significant decrease in MDA and increase in GSH levels were observed in this group.Conclusion: Montelukast appears to exert a protective activity in WAS inducedurinary bladder injury by inhibiting inflammatory and oxidative activity.