Objective Using cochlear metabolomics to study the mechanisms underlying age-related hearing loss in rat.Methods A total of 30 rats with 2-month-old(young group)and 14-month-old(old group)were select-ed,with 15 rats in each group.The auditory function in each group was detected by auditory brainstem response(ABR),the morphology of cochlear tissue in both groups was observed using HE staining,and the oxidative stress status of cochlear tissue was detected by flow cytometry.Five rats/groups were selected for metabolomic examina-tion of cochlear tissue by untargeted ultra-high performance liquid chromatography-mass spectroscopy(LC-MS/MS)to analyze the metabolic differences in the aging cochlea.Results Compared with young group,ABR detection of tone burst at 8,16,and 32 kHz and click response thresholds were significantly higher in old group(P＜0.05),HE staining showed cochlear senescence-related vascular stripe atrophy(P＜0.05),and flow cytometric techniques suggested significantly higher levels of oxidative stress in old group(P＜0.05).Metabolomics detection revealed that a total of 124 differential metabolites were identified in the cochlea of the old group,of which 16 metabolites in-cluding sphingosine,all-trans-retinoic acid,and oleamide were significantly upregulated,while the levels of 108 me-tabolites such as purine,taurine,thiamine,and proline and its derivatives were significantly decreased.The results suggested that physiopathological mechanisms such as protein synthesis and catabolism,sphingolipid metabolism,purine metabolism,oxidative stress-related signaling,cell death,and coenzyme biosynthesis may be involved in co-chlear aging.Conclusion Cellular senescence and cochlear metabolic dysfunction may be important mechanisms of age-related hearing loss.