BTB and CNC homology 1 (Bach1) is a transcriptional repressor of anti-oxidative enzymes, such as heme oxygenase-1 (HO-1). Oxidative stress is reportedly involved in insulin secretion impairment and obesity-associated insulin resistance. However, the role of Bach1 in the development of diabetes is unclear. HO-1 expression in the liver, white adipose tissue and pancreatic islets was markedly up-regulated in Bach1-deficient mice. Unexpectedly, glucose and insulin tolerance tests showed no differences in obese wild-type (WT) and obese Bach1-deficient mice, after high-fat diet loading for 6 weeks, suggesting minimal roles of Bach1 in the development of insulin resistance. In contrast, Bach1 deficiency significantly suppressed alloxan-induced pancreatic insulin content reduction and the resultant glucose elevation. Furthermore, TUNEL-positive cells in pancreatic islets of Bach1-deficient mice were markedly decreased, by 60%, compared with those in WT mice. HO-1 expression in islets was significantly up-regulated in alloxan-injected Bach1-deficient mice, while expression of other anti-oxidative enzymes, catalase, superoxide dismutase and glutathione peroxidase, was not changed by either alloxan administration or Bach1 deficiency. Our results suggest that Bach1 deficiency protects pancreatic β-cells from oxidative stress-induced apoptosis and that the enhancement of HO-1 expression plays an important role in this protection.