Previous investigations have indicated that reduced erythrocyte deformability may be an important factor contributing to the development of atherosclerosis, and endogenous asymmetric dimethylarginine (ADMA) might be an important contributor to reduction of erythrocyte deformability in atherosclerosis. In this study, the effect of 3,4,5,6-tetrahydroxyxanthone (1), a kind of polyphenolic compound, on erythrocyte deformability in apolipoprotein E-deficient (apoE-/-) mice was evaluated. After treatment with compound 1 (10 or 20 mg/kg per day) for 4 weeks, erythrocyte deformability, antioxidant enzymes activity, erythrocyte dimethylarginine dimethylaminohydrolase (DDAH) activity, the plasma level of ADMA and malondialdehyde (MDA) level were determined. Treatment with compound 1 (10 or 20 mg/kg) increased erythrocyte deformability, antioxidant enzymes activity concomitantly, a decrease in the plasma levels of MDA and ADMA, and an increase in erythrocyte DDAH activity. The present result suggests that the beneficial effect of 1 on the erythrocyte deformability, besides inhibiting lipid peroxidation, may be related to reduction of ADMA concentration via an increase in DDAH activity.