An antibacterial drug, ciprofloxacin, has been reported to modulate the inflammatory and immune responses on monocytes. Our objective is to evaluate the effectiveness of ciprofloxacin in the prevention of myringosclerosis that is created by myringotomy in rats and to compare it with prednisolone. In this study, 24 healthy Sprague-Dawley type rats of age 3-4 months and 250-300 g weight were used. Rats have been divided into three random groups. Topical ciprofloxacin was administered to the rats in the first group and topical prednisolone was administered to the rats in the third group; no medication was applied to their opposite ears and they were determined as control group. Prednisolone was administered to one ear of the rats and ciprofloxacin was administered to their opposite sides in the second group. After bilateral myringotomies the treatments were applied for 20 days as five drops two times a day. Otomicroscopic examination was made on the 10th day and reperforations were made when necessary. Rats were killed on the 21st day and temporal bone dissections were done. When we evaluate in terms of myringosclerosis and tympanic membrane thickness, in the first group, myringosclerosis and thickness have been observed in two of seven ears (28.6%) where ciprofloxacin was administered and in five of the seven ears (71.4%) where no treatment was applied. In the second group where prednisolone and ciprofloxacin were compared, myringosclerosis and thickness have been observed in six of the ten ears (60.0%) where prednisolone was administered and in four of the ten ears (40.0%) where ciprofloxacin was administered. In the third group, myringosclerosis and thickness have been observed in three of seven ears (42.9%) where prednisolone was administered and in four of the seven ears (57.1%) where no treatment was applied. All histopathological evaluations were made by one pathologist in a blinded manner. In our study, the effect of the ciprofloxacin and prednisolone was similar in preventing the experimental myringosclerosis and TM thickness in rats. When compared with the control groups, this preventive effect was more obvious in the ciprofloxacin treatment group than that of prednisolone.