Abstract: The objective of the study is to investigate the effect of theabrownin on the immunohistochemistry of brain tissue in aging mice, screen the differential metabolites and analyze the metabolic pathways involved. A mouse aging model was established by subcutaneous injection of D-galactose in mice. Immunohistochemical and UHPLC-QE-MS metabolomics techniques were used to detect brain samples of normal control mice, D-galactose model mice and theabrownin-treated (pretreatment and treatment) mice. The results showed that the areal density of choline acetyltransferase positive expression was significantly increased (P<0.05) after theabrownin intervention. Prophylactic administration of theabrownin could significantly regulate 17 metabolites in brain tissue of aging mice, mainly involving glycerophospholipid metabolism, histidine metabolism, TCA cycle, glyoxylate and dicarboxylate metabolism and beta-alanine metabolism. Theabrownin treatment could significantly regulate 32 metabolites in brain tissue of aging mice, mainly involving glycerophospholipid metabolism, histidine metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine degradation, phenylalanine, tyrosine and tryptophan biosynthesis. Carnosine, LysoPC(P-18:1(9Z)), PS(20:5(5Z,8Z,11Z,14Z,17Z)/18:1(9Z)), PC(15:0/15:0), D-arabinose 5-phosphate, cholesterol sulfate, adenosine diphosphate ribose, glycerophospholipid metabolism and histidine metabolism were common in the theabrownin pretreatment and theabrownin treatment groups. Theabrownin can play an anti-aging role by regulating lipid metabolism, energy metabolism, amino acid metabolism and other processes in mice.