To explore the effect of strong noise on cognitive function and stress hormones, biochemical metabolism enzymes, neuropeptide etc in theserum of guinea pigs, and screen the sensitive bio-markers of noise-induced cognitive impairment.Twenty-four guinea pigs were randomly divided into the noise exposure group and the control group, after the white noise at 120 dB continuously exposed for 4 h. Using Morris water maze to detect the cognitive ability of guinea pigs, and using Elisa kits to detect the content of neuropeptide Y (NPY), neuropeptide P (NPP), neuroglobin (NGB), c-reactive protein (CRP), cortisol (CORT), adrenocorticotropic hormone (ACTH), corticotropin releasing hormone (CRH) and epinephrine (E), norepinephrine (NE), angiotensin Ⅱ (AngⅡ), aldosterone (ALD), oxytocin (OT), vasopressin (VAP), alanine aminotransferase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) in the serum of guinea pig. Multiple regression analysis was used to evaluatethe sensitive indexes for the influence of cognitive function.Morris water maze test indicated that the average escape latency of noise exposure group extended obviously, cross platform number and residence time in target quadrant were significantly reduced compared with control group(P<0.01). Elisa results showed that the content of the biochemical indexes above of noise exposure grouphad significant statistical difference except AngⅡ compared with control group(P<0.01), among them, the content of CORT, NPY, NE, NGB, NPP, CK changed obviously and contributed greatly to cognitive in turn.Strong noise at 120dB continuous exposure for 4 h caused a significant decline on cognitive function of guinea pigs, it might be related to the abnormal levels of the physiological and biochemical indexes in serum such as stress hormones, biochemical metabolism enzyme, neuropeptides, neuroglobin etc, and we preliminarily filtrated several sensitive index associated with noise-induced cognitive impairment, including CORT、NPY、NE、NGB、NPP and CK.