In this study, (1)H NMR-based metabonomics was applied to evaluate the beneficial effects of cordycepin (3'-deoxyadenosine), a natural monomer compound, on endogenous metabolic profiles of liver and plasma from hyperlipidemic Syrian golden hamsters. Hyperlipidemia was successfully established in hamsters fed by a high-fat diet for 2 weeks. The hyperlipidemic hamsters were treated with an oral administration of simvastatin (2 mg kg(- 1)) or cordycepin (140 mg kg(- 1)) for consecutive 4 weeks. The metabolic profiles of plasma and intact liver tissues were established using (1)H NMR spectroscopy. The results showed higher contents of lipids (triglyceride and cholesterol), lactate, acetate, alanine, glutamine together with lower contents of choline-containing compounds (e.g. phosphocholine, phosphatidylcholine, and glycerophosphocholine), glucose, and glycogen in plasma and liver samples from hyperlipidemic hamsters than those in controls. Cordycepin afforded a little lipid-regulating activity on plasma but more beneficial effects on liver, implicating that cordycepin might have a protective effect on liver under fatty liver condition.