The purpose of the present study was to investigate the effect of vitamin E supplementation on autoimmune disease in New Zealand blackxNew Zealand white F1 (NZB/W F1) female mice fed an oxidised oil diet. First, 5-month-old mice were fed an AIN-76 diet containing either 150 g fresh soyabean oil/kg (15S), 50 g fresh soyabean oil/kg + 100 g oxidised frying oil/kg (5S10F) or 5S10F supplemented with all-rac-alpha-tocopheryl acetate at 275 mg/kg diet level (5S10F5E) or 550 mg/kg (5S10F10E), respectively, in experiment 1. The results showed that mice fed the 5S10F10E diet had a lower anti-double-stranded DNA IgG antibody level and a longer lifespan than those fed the 15S and 5S10F diets. Therefore, the 5S10F and 5S10F10E treatments were repeated in experiment 2 for further analysis. The results showed that vitamin E supplementation in the oxidised oil significantly decreased thiobarbituric acid-reactive substance values in the kidney and spleen of NZB/W F1 mice. Interferon-gamma and IL-6 production by mitogen-stimulated splenocytes decreased in mice fed the 5S10F10E diet, whereas the secretion of IL-2 and IL-10 was not affected. The percentage of T-cells was significantly higher and that of MHC class II-bearing cells was lower in the spleens of the 5S10F10E group. The 5S10F10E group had a significantly higher linoleic acid (18 : 2n-6) composition than the 5S10F diet group. Therefore, vitamin E supplementation in oxidised oil might decrease oxidative stress, anti-double-stranded DNA IgG antibody, regulate cytokines and lymphocyte subsets, and subsequently alleviate the severity of autoimmune disease such as systemic lupus erythematosus under oxidative stress.