OBJECTIVE: To investigate the metabolic pathogenesis in subjects with subjective tinnitus (ST) having kidney deficiency pattern (KDP) (ST/KDP) in terms of Traditional Chinese Medicine. METHODS: Three groups of subjects, including healthy individuals, subjects with ST/KDP, and subjects who were healthy initially and then developed ST/KDP one year later (healthy -> ST/KDP), were recruited for this study. Serum metabolic profiles of all subjects were analyzed using ultra-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. The metabolic characteristics of the ST/KDP subjects were determined, and the corresponding biomarkers were predicted. The metabolomics data from the healthy -> ST/KDP subjects were collected for further verification. RESULTS: Twelve metabolites in the ST/KDP subjects were different from those of the healthy control subjects. Of these metabolites, according to the prediction, except for octanoic acid, other metabolites might characterize ST/KDP. Ten metabolites at the outcome ST/KDP stage were different from those at the initial (control) stage. Through the comparison of these metabolites with the predicted metabolites, five common metabolites, including upregulated glutamate, serotonin, orotic acid and 8-oxoguanine, as well as downregulated taurine, were found. These common metabolites were significantly associated with canonical pathways including calcium signaling, gamma-aminobutyric acid (GABA) receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling. CONCLUSION: The metabolic pathogenesis in ST/ KDP subjects was characterized by upregulated glutamate, serotonin, orotic acid and 8-oxoguanine, as well as downregulated taurine, additionally, perturbations of calcium signaling, GABA receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling. (C) 2018 JTCM. All rights reserved.