In the present study, novel preventive effects of repeated low-dose radiation exposure on diabetes-induced cardiac inflammation and cardiac damage were investigated. C57BL/6J mice were given multiple low doses of streptozotocin (STZ, 60 mg/kg × 6) to generate type 1 diabetes. A week after the last STZ injection, hyperglycemic mice were diagnosed and treated with and without whole-body low-dose radiation exposure (25 mGy X rays) once every 2 days for 2, 4, 8, 12 and 16 weeks. Diabetes caused significant increases in cardiac inflammation, shown by time-dependent increases in mRNA and protein expressions of interleukin 18 (IL-18), tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), plasminogen activator inhibitor 1 (PAI-1), and monocyte chemoattractant protein 1 (MCP-1). Repeated exposure of control mice to low-dose radiation caused mild increases in these inflammatory factors, except for ICAM-1. Repeated exposure of diabetic mice to low-dose radiation significantly reduced diabetes-increased cardiac expression of IL-18, TNF-α, MCP-1 and PAI-1 at both the mRNA and protein levels. Furthermore, cardiac histopathological abnormalities, oxidative damage and fibrosis were significant in diabetic mice but to a lesser extent in diabetic mice with repeated low-dose radiation exposure. These results suggest that although low-dose radiation contributes to mild cardiac inflammation in control mice, it can significantly reduce diabetes-induced cardiac inflammation and associated pathological changes. Therefore, low-dose radiation may potentially become a novel approach to the prevention of diabetic cardiovascular complications.