〔Abstract〕 Objective To investigate the effect of(exchange protein directly activated by cAMP-1) on inner ear hair cell injury with noise-induced hearing loss and its potential mechanism in rats. Methods Twenty Specific pathogen-free(SPF) Sprague-Dawley(SD) rats were randomly divided into normal control group and noise exposure group. The rats of noise exposure were exposed to 4 kHz at 101 dB sound pressure level(SPL) for 8 h. Auditory brainstem responses(ABR)were measured in animals before noise exposure and 24 h after noise exposure. Surface preparation, transmission electron microscopy and immunohistochemistry were performed on cochlea tissuesto elucidate changes in Epac expression in rat after noise exposure. The expression levels of Epac1、Rap1、CaMK-Ⅱ、Bax、Bcl-2、cleaved caspase3(CC3) and cleaved caspase9(CC9)were analyzed using Western blot. Results There was found a stable temporary threshold shift after noise exposure(P<0.05). The missing of outer hair cells occurred after noise exposure(P<0.05). Transmission electron microscopy indicated that the epidermis plate of HCs was partially dissolved, with loss or fusion of stereocilia, some HC organelles showed serious injuries after noise exposure. Epac1 immunostaining intensities were substantially enhanced in OHCs after noise exposure(P<0.05). The expression levels of Epac1, CaMK-Ⅱ and Rap1 protein were significantly up-regulated after noise exposure(P<0.05). The expression level of Bcl-2 was significantly down-regulated after noise exposure(P<0.05). The expression levels of Bax, CC3 and CC9 were significantly up-regulated after noise exposure(P<0.05). Conclusion Epac1-Rap1 signaling pathway mediates the early pathological damage in noise-exposed cochlea, and participates in the regulation of inner ear hair cells apoptosis. Epac1-Rap1 pathway is expected to become a new target for intervention in noise-induced hearing loss.