Objective To investigate the prophylactic effect of low calcium concentration perilymph on noise-induced hearing loss. Methods Forty guinea pigs with normal hearing weighing 250-350 g were assigned to five groups (8 in each group): (1) Ca 2+ -deficient perilymph perfusion (CDP) for 2 h; (2) white noise (120 dB SPL) exposure (WNE) only for 1 h, (3) combination of calcium-deficient perilymph perfusion and white noise (120 dB SPL) exposure (WNE+CDP); (4) normal artificial perilymph (NAP) perfusion for 2 h; and (5) white noise exposure + normal artificial perilymph perfusion (WNE+NAP) for 2 h. Compound action potentials (CAP) evoked by click was recorded from round window every 15 min. The cochleae from 5 animals in each group were examined with scanning electron microscope. Results The CAP for group 1 experienced a threshold shift (TS) of 15-26 dB, while group 2 yielded a 46-59 dB TS and group 3 a 37-45 dB TS; no threshold shift occurred in group 4. The CAP TS in group 5 was 33-64 dB. The CAP TS of group 3 was less than that of group 2. After one hour of noise exposure, the CAP TS of group 3 were 45.92±2.90 dB and 59.30±3.95dB in group 2. There were significant differences ( P <0.05) between groups 3 and 2. The CAP TS of group 3 was less than that of group 5 at the points of 1, 1.5 and 2 h after noise exposure. There was a significant difference between groups 3 and 5 ( P <0.01). Stereocilia of 89 OHC_3 were in disarray in five cochleae after noise exposure in group 2. The cuticular plates of 8 OHC_ 2,3 sank and the stereocilia became fused in only one animal cochlea after noise exposure in group 3 combined with low calcium perilymph perfusion. Conclusions Low calcium concentration appears to participate in preventing noise-induced hearing loss and the rising of calcium concentrations in inner hair cells after noise exposure, which may have been due to the opening of calcium channels in inner hair cells during noise exposure. The mechanism of the prophylactic effect might be caused by a lower calcium concentration in inner hair cells in the cochlea attenuating the influence of noise exposure on hearing loss; calcium deficient perilymph perfusion prevented calcium accumulation in inner hair cells of the cochlea. The motility of the OHCs might be partially inhibited by low calcium concentration that reduced noise-induced hearing loss in turn. Objective To investigate the prophylactic effect of low calcium concentration perilymph on noise-induced hearing loss. Methods Forty guinea pigs with normal hearing weighing 250-350 g were assigned to five groups (8 in each group): (1) Ca 2+ -deficient (2) white noise (120 dB SPL) exposure (WNE) only for 1 h, (3) combination of calcium-deficient perilymph perfusion and white noise (120 dB SPL) exposure (WNE + (4) normal artificial perilymph (NAP) perfusion for 2 h; and (5) white noise exposure + normal artificial perilymph perfusion (WNE + NAP) for 2 h. round the window every 15 min. The cochleae from 5 animals in each group were examined with scanning electron microscope. Results The CAP for group 1 experienced a threshold shift (TS) of 15-26 dB, while group 2 yielded a 46-59 dB TS and group 3 a 37-45 dB TS; no threshold shift occurred in group 4. The CAP TS in group 5 was 33-64 d B. The CAP TS of group 3 was less than that of group 2. After one hour of noise exposure, the CAP TS of group 3 were 45.92 ± 2.90 dB and 59.30 ± 3.95 dB in group 2. There were significant differences (P < 0.05) between groups 3 and 2. The CAP TS of group 3 was less than that of group 5 at the points of 1, 1.5 and 2 h after noise exposure. There was a significant difference between groups 3 and 5 (P <0.01) . Stereocilia of 89 OHC_3 were in disarray in five cochleae after noise exposure in group 2. The cuticular plates of 8 OHC_2,3 sank and the stereocilia were fused in only one animal cochlea after noise exposure in group 3 combined with low calcium perilymph perfusion . Conclusions Low calcium concentration appears participate in preventing noise-induced hearing loss and the rising of calcium concentrations in inner hair cells after noise exposure, which may have been due to the opening of calcium channels in inner hair cells during noise exposure. The mechanism of the prophylactic effect might be caused by a lower calcium concentration in inner hair cells in the cochlea attenuating the influence of noise exposure on hearing loss; calcium deficient perilymph perfusion prevented calcium accumulation in inner hair cells of the cochlea. The motility of the OHCs might be potential controlled by low calcium concentration that reduced noise-induced hearing loss in turn.