Introduction: Myringosclerosis, one of the most common complications of ventilation tube placement, is a kind of tympanosclerosis and is defined as subepithelial hyalinization of the tympanic membrane. There are two arguments in the development of myringosclerosis: inflammation triggering the development of myringosclerosis and free oxygen radicals released during inflammation causing myringosclerosis. Objective: The aim of the present study was to explore the effects on the development of myringosclerosis of mitomycin, which has anti-inflammatory effects, and trimetazidine, which is believed to inhibit free oxygen radicals when given systemically. Materials and Method: The study was carried out on rabbits. Animals were divided into five groups, with six rabbits in each group: three control groups (paracentesis only, paracentesis + tube placement, and no intervention), a trimetazidine group, and a mitomycin group. Mitomycin (0.4 mg/mL) and trimetazidine (20 mg/mL) were applied topically to the tympanic membrane, and the presence and degree of sclerosis were graded histopathologically after Masson's trichrome staining. Results: In the histopathologic examination, sclerosis that developed in the tympanic membranes of rabbits that had undergone paracentesis or paracentesis plus tube application or received trimetazidine was significantly more extensive than sclerosis in the membranes of unoperated animals and those that had been administered mitomycin. Conclusions: Paracentesis in rabbits, independent of tube placement, causes sclerosis of the tympanic membrane. Results show that topical use of mitomycin, due to its anti-inflammatory effect, had alleviating effects on myringosclerosis, whereas topical trimetazidine did not. © 2008 The Canadian Society of Otolaryngology-Head & Neck Surgery.