BACKGROUND : Polygonum Multiflorum Thunb(PMT) has multiple biological effects, such as anti-inflammatory, lipid-lowering, anti-aging and so on. Therefore, D-galactose-induced aging mice were used to study the effect of PMT on fatty acid metabolism and its underlying mechanism. METHODS : C57BL/6 male mice were randomly divided into normal group, aging model group, PMT intragastrical administration group (high, Medium, low); model group and PMT intragastrical administration group Daily intraperitoneal injection D-galactose 800 mg·ml- 1·Kg- 1 to establish subacute aging model; PMT intragastrical administration group at the same time to intragastrical PMT extract (1 g·ml- 1·Kg- 1, 0.6 g·ml- 1·Kg- 1, 0.3 g·ml- 1·Kg- 1), normal group injection and intragastrical equivalent saline for 60 consecutive days. By detecting the oxidation index of liver to judge the efficacy of PMT, gas chromatography-mass spectrometry (GC-MS) analysis was used to quantitatively analyze the fatty acid content in liver. RESULTS : Finally, we found that PMT improved the enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in aging mice, and reduce the enzyme activity of malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The content of fatty acids such as C18:1, C18:2, C18:3 N3, C20:2 and C20:3 N3 decreased significantly in senescent mice (P < 0.05) as evidenced by GC-MS analysis, whereas, these fatty acids increased significantly after treatment of PMT (P < 0.05). CONCLUSIONS : PMT improves the content of liver fatty acids in aging mice induced by D-galactose through, enhancing the activity of anti-oxidant enzymes.