Chromium supplementation has been proposed to promote the action of insulin and the lowering of blood glucose levels in diabetic patients. However, the molecular mechanism by which chromium increases insulin sensitivity is not known. Using U937 monocytes as a cell culture model, this study demonstrates that chromium inhibits the secretion of TNF-a, a cytokine known to inhibit the sensitivity and action of insulin. U937 cells were cultured with high levels of glucose (mimicking diabetes) in the presence or absence of chromium chloride in the medium at 37 degreesC for 24 h. This study demonstrates that chromium supplementation prevents the increase in TNF-a levels and oxidative stress caused by the high levels of glucose in cultured U937 monocytic cells. Similarly, chromium supplementation prevented elevated TNF-a secretion and lipid peroxidation levels in H2O2-treated U937 cells. This study demonstrates for the first time that chromium supplementation inhibits TNF-a secretion in U937 monocytes cultured in high-glucose medium, which appears to be mediated by its antioxidative effect. This provides evidence for a novel molecular mechanism by which chromium supplementation may increase insulin sensitivity and glycemic control in diabetic patients.