In type 1 diabetes, diabetic bone disease (DBD) is characterized by decreased bone mineral density, a state of low bone turnover and an increased risk of fracture. Animal models of DBD demonstrate that acquired alterations in trabecular and cortical bone microarchitecture contribute to decreased bone strength in diabetes. With anti-collagenolytic and anti-inflammatory properties, tetracycline derivatives may prevent diabetes-related decreases in bone strength. To determine if doxycycline, a tetracycline class antibiotic, can prevent the development of DBD in a model of long-term diabetes, male DBA/2J mice, with or without diabetes, were treated with doxycycline-containing chow for 10 weeks (dose range, 28-92 mg/kg/day). Long-term doxycycline exposure was not deleterious to the microarchitecture or biomechanical properties of healthy bone in male DBA/2J mice. Doxycycline treatment also did not prevent or alleviate the deleterious changes in trabecular microarchitecture, cortical structure, and biomechanical properties of bone induced by chronic diabetes.