We conducted an animal experiment to assess the effect of adding pentoxifylline to amikacin to prevent amikacin-induced ototoxicity. Tis research was conducted on 24 rats arranged in four groups of 6. One group was injected with 200 mg/kg of intramuscular amikacin once daily for 14 days (AMK-only group). Another received 25 mg/kg of oral pentoxifylline and 200 mg/ kg of intramuscular amikacin once daily for 14 days (PTX-AMK 14/14 group). A third group received 25 mg/kg of oral pentoxifylline for 28 days and 200 mg/ kg of intramuscular amikacin once daily for 14 days on days 15 through 28 of the pentoxifylline regimen (PTX-AMK 28/14 group). Finally, a control group was administered 1 ml/day of 0.5% carboxymethyl cellulose for 28 days. Transient otoacoustic emissions (TOAEs) were statistically analyzed and serum urea and creatinine levels were measured before and afer treatment. We found no signifcant differences in TOAEs among the groups at the study’s onset, but afer the experiment, TOAEs disappeared in all frequency bands in the AMK-only and PTX-AMK 14/14 groups. However, TOAEs were preserved in the PTX-AMK 28/14 group. In addition, the serum urea and creatinine levels in the PTX/AMK 28/14 group were signifcantly lower than the levels in the other two treatment groups (p < 0.05 for all), but not signifcantly different from those of the control group. We conclude, therefore, that 28 days of pentoxifylline treatment exerted a protective effect against amikacin-induced ototoxicity in rats