Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints. This study investigated whether or not a diet deficient in vitamin E is a possible risk factor in the development of RA and evaluated the efficacy of antioxidant supplementation. Male DBA/1J mice were maintained on either a control diet (C) or a vitamin E-depleted (-VE) diet for 4 weeks before arthritis induction. The mice in the control group were subdivided into the control group (C/C), the 0.05% alpha-tocopherol-supplemented group (C/+VE), and the 0.5% quercetin-supplemented group (C/+Q). The vitamin E-depleted group was subdivided into the -VE group (-VE/-VE), the 0.05% alpha-tocopherol-supplemented group (-VE/+VE), and the 0.5% quercetin-supplemented group (-VE/+Q) (in total, six groups, 27 mice per group). The mice were maintained on the experimental diets for 9 weeks. Study results indicate that the -VE/-VE group showed higher joint tissue tumor necrosis factor-alpha and interleukin-1beta mRNA expressions, whereas alpha-tocopherol or quercetin supplementation reduced tissue cytokine mRNA levels to values comparable to those of the C/C group. The mice fed the -VE/-VE diet exhibited higher levels of circulating macrophage chemoattractant protein 1, nitric oxide, and prostaglandin E(2) compared to those in other groups. Supplementation with alpha-tocopherol or quercetin in mice fed -VE diet decreased these markers similar to those of the mice in the C/C group. No supplementation effect was observed, however, in the mice fed with the control diet prior to RA induction. These results suggest that dietary deficiency of vitamin E increases inflammatory responses and that antioxidants successfully suppress the inflammatory responses. However, significant clinical improvement may require longer observation.