To evaluate the protective effect of intravesical oxybutynin on the ultrastructure of rabbits with detrusor overactivity (DO). Seventeen North Folk male rabbits were distributed into three groups: GI (n = 5) used as control, GII (n = 5), and GIII (n = 5) with DO. One animal from GII and one from GIII were excluded because they did not develop DO. In GIII, the animals were treated with daily intravesical application of 0.5 mg/Kg of oxybutynin for 30 days. Bladder weight was significantly higher in animals from GII and GIII as compared to GI. After 30 days, cystometric study revealed that vesical capacity was significantly decreased in GII and GIII. Detrusor pressure was significantly higher in GII. Electron microscopy showed increase of intercellular space, cell junctions and caveolae areas asymmetries, mitochondria and cellular degeneration in GII, while in GIII, these alterations have improved after a 30-day treatment. Animals treated with intravesical oxybutynin presented ultrastructural aspect similar to normal.