Cisplatin ototoxicity is a major dose-limiting factor in the treatment of several neoplasms. Dexamethasone and vitamin E are two slow-acting free radical cleaners, and they have been shown to ameliorate nephrotoxicity and endothelial cell damage in animals receiving cisplatin. The purpose of the study was to determine the effectiveness of vitamin E and dexamethasone as an otoprotectant intratympanically. Prospective, randomized controlled trial in the rat model. Wistar rats were sedated using 50 mg/kg intraperitoneal ketamine and 7.5 mg/kg xylazine. Baseline auditory brainstem response (ABR) testing was performed in response to clicks and 4.8-, 12-, 16-kHz tone bursts. After auditory thresholds were determined, the animals received intraperitoneal drug administration according to one of the four groups. The rat groups received (group I) % 09 NaCl solution intratympanically (IT), (group II) cisplatin (20 mg/kg) only intraperitoneally (IP), (group III) dexamethasone (0.1-0.3 ml) IT and (group IV) vitamin E solution (0.1-0.3 ml) IT followed after 30 min by 20 mg/kg cisplatin. After the 3-day follow-up, ABR testing was performed and threshold changes were recorded. Group II animals showed marked hearing loss with average threshold shifts of 39.7 ± 1.4 dB for clicks, 7.3 ± 2.6 dB at 4 kHz, 8.4 ± 1.6 dB at 8 kHz, 71.1 ± 4.2 dB at 12 kHz and 71.9 ± 5.9 dB at 16 kHz. No significant loss was observed in group III with shifts of 1.60 ± 1.3 dB, 4.75 ± 2.4 dB, 8.7 ± 3.4 dB, and 4.3 ± 2.1 dB for clicks and tone bursts at 4.8, 12, and 16 kHz, respectively. And similar findings were observed in group IV with shifts of 3.3 ± 1.4 dB, 7.2 ± 2.1 dB, 10.8 ± 2 dB, and 13.3 ± 3.1 dB for clicks and tone bursts at 4.8, 12, and 16 kHz, respectively. Significant protection was seen in group III and IV animals compared with group II animals. There is no side effect in IT administration of vitamin E and dexamethasone for hearing functions and two of them appear to have a easier, safer, usable protective effect against cisplatin ototoxicity.