The anti-diabetic effects of COB extract, that its major components are polyphenols, and that it produces antioxidant, anti-hyperglycemic and anti-hyperlipidemic effects in STZ-diabetic rats were investigated. However, the influence of COB polyphenols on the expression of genes involved in these biological effects in diabetic rat tissues have been not investigated. Therefore, in this study, we fed STZ diabetic-male ICR mice with a long-term COB treatment (500 mg/kd body weight, for 10 weeks) and investigated the effects of COB treatment on the target gene expression levels in liver and kidney tissues, including the oxidative stress genes of GPX-2, GST A1 and SOD-1. The expression levels of target genes in mouse liver and kidney tissues were quantified by cDNA microarray analysis. Differences in gene expression were considered to be significant at a ratio of at least 2.0. After 10 weeks of feeding, the COB-treated diabetic mice (DB) had a significant decrease in blood glucose, total cholesterol and triglyceride level compared to the control diabetic mice (DC). A series of oxidative stress genes of GPX-2, GST A1 and SOD-1 was up-regulated in DC, and showed a higher than 2.0 fold change as compared to normal mice. The DB group showed its antioxidant effect by decreasing fold change values in GPX-2, GST A1 and SOD-1 to that of the DC group. These results have suggested that COB treatment has a positive regulatory response to oxidative stress genes in various tissues in diabetic mice. Consequently, COB is likely to be sufficiently safe for daily use in prevention and treatment of diabetes and other non-communicable diseases.