Epidemiological studies have shown lower levels of chromium among men with diabetes and cardiovascular disease (CVD) compared with healthy control subjects. The mechanism by which chromium may decrease the incidence of CVD and insulin resistance is not known. Using erythrocytes as a model, this study demonstrates that chromium inhibits the glycosylation of proteins and oxidative stress, both risk factors in the development of CVD. Erythrocytes were treated with high levels of glucose (mimicking diabetes) in the presence or absence of chromium chloride in the medium at 37 degrees C for 24 hours. Chromium supplementation prevented the increases in protein glycosylation and oxidative stress caused by the high levels of glucose in erythrocytes. This study demonstrates for the first time that chromium supplementation inhibits protein glycosylation in erythrocytes exposed to high glucose medium, which appears to be mediated by its antioxidative effect. This provides evidence for a novel mechanism by which chromium supplementation may decrease incidence of CVD in diabetic patients.