Objective To establish an animal model of sudden onset sensorineural hearing loss (SSNHL) to study its mechanisms. Materials and methods The inner ear was exposed to 3-nitropropionic acid at 0.5 mol/L (3-NP (H)) and 0.3 mol/L (3-NP (L)) through the round window membrane for 30 minutes in 50 male guinea pigs. Thresholds of auditory brainstem responses(ABR) were established before the treatment and retested at 4 hours, 1 day, 3 days and 6 days following 3-NP exposure. Control animals were treated with phosphate buffered saline (PBS) and their ABRs were retested at 4 hours and 1 day after the treatment. Animals were monitored for nystagmus and postural signs of vestibular dysfunction, using a digital video camera, following the treatment procedure. Specimens were taken at 12 hours, 1 day, 3 days and 7 days following 3-NP(H) exposure and embedded in JB4 for light microscopy observation. Results ABRs were lost in all animals tested at 4 hours following 3-NP (H) exposure. The rate of complete ABR loss decreased as post-treatment test time increased. ABRs were lost in 80% (4/5) of the animals at 1 day after exposure to 3-NP (L). Spontaneous horizontal nystagmus with a fast phase away from the treated ear developed in all 3-NP (H)-treated animals and in 20 % ( 1/5) of the animals exposed to 3-NP (L), except for the one treated bilaterally. Various degree of postural disturbances consistent with unilateral vestibular dysfunction, such as spontaneous barrel rolling towards the exposure side while walking, were seen in all animals exposed to 3-NP(H) and 40% (2/5) of animals exposed to 3-NP(L), except for the one animal treated bilaterally, which showed no signs of imbalance. Both nystagmus and postural disturbances resolved in 2 days following 3-NP exposure. Histological study showed temporary edema tin the organ or Corti, Claudius cells and the inner sulcus cells 3 days after 3-NP (H) treatment. Enlargement of intercellular space in the spiral prominence was first noticed at 12 hours post-3-NP (H) exposure, progressed at day 3 and recovered at day 7. Vacuoles in the cellular plasm and nucleus was seen as early as at 12 hours post-3-NP exposure in the spiral ganglion cells, and signs of degeneration were visible at day 7. Conclusion Inner ear exposure to 3-NP through the round window membrane appears to reproduce clinic manifestations and may serve as a legitimate animal model of SSNHL Objective To establish an animal model of sudden onset sensorineural hearing loss (SSNHL) to study its mechanisms. Materials and methods The inner ear was exposed to 3-nitropropionic acid at 0.5 mol / L (3-NP (H) L (3-NP (L)) through the round window membrane for 30 minutes in 50 male guinea pigs. Thresholds of auditory brainstem responses (ABR) were established before the treatment and retested at 4 hours, 1 day, 3 days and 6 days The following 3-NP exposure. Control animals were treated with phosphate buffered saline (PBS) and their ABRs were retested at 4 hours and 1 day after the treatment. Animals were monitored for nystagmus and postural signs of vestibular dysfunction, using a digital video camera, following the treatment procedure. Specimens were taken at 12 hours, 1 day, 3 days and 7 days following 3-NP (H) exposure and embedded in JB4 for light microscopy observation. Results ABRs were lost in all animals tested at 4 hours following 3 -NP (H) exposure. The rate of complet ABRs were lost in 80% (4/5) of the animals at 1 day after exposure to 3-NP (L). Spontaneous horizontal nystagmus with a fast phase away from the treated ear developed in all 3-NP (H) -treated animals and in 20% (1/5) of the animals exposed to 3-NP (L), except for the one treated bilaterally. Various degree of postural disturbances consistent with unilateral vestibular dysfunction, such as spontaneous barrel rolling towards the exposure side while walking, were seen in all animals exposed to 3-NP (H) and 40% (2/5) of animals exposed to 3-NP (L), except for the one Both nystagmus and postural disturbances resolved in 2 days following 3-NP exposure. Histological study showed temporary edema tin the organ or Corti, Claudius cells and the inner sulcus cells 3 days after 3-NP (H) treatment. Enlargement of intercellular space in the spiral prominence was first noticed at12 hours post-3-NP (H) exposure, progressed at day 3 and recovered at day 7. Vacuoles in the cellular plasm and nucleus was seen as early as at 12 hours post-3-NP exposure in the spiral ganglion cells, and signs of degeneration were visible at day 7. Conclusion Inner ear exposure to 3-NP through the round window membrane appears to reproduce clinic manifestations and may serve as a legitimate animal model of SSNHL