We previously reported that peripheral injection of brain-derived neurotrophic factor (BDNF) exhibits hypophagic and hypoglycemic effects in obese hyperglycemic animals, indicating its antiobesity and antidiabetic effects. Since previous studies were focused on the effect of BDNF on overt diabetic animals with severe hyperglycemia, there was no evidence whether BDNF is effective or not for the development of diabetes in prediabetic animal models. Therefore, we evaluated the effect of BDNF on preventing the development of diabetes in db/db mice. First, we characterized age-related changes in the pathophysiology of diabetes in db/db mice. We chose 8 week-old db/db mice as the early diabetic stage (early intervention study) and 4 week-old db/db mice as the prediabetic stage (prevention study). Next, we examined the effects of BDNF on the progression of diabetes in early diabetic db/db mice. In the early intervention study using 8 week-old db/db mice, intermittent treatment with BDNF prevented the deterioration in hyperglycemia. Lastly, we examined the preventive effects of BDNF on the development of diabetes in prediabetic db/db mice. In the prevention study using 4 week-old db/db mice, treatment with BDNF prevented the age-related increase in blood glucose concentration. These results showed for the first time that BDNF prevents the development of diabetes in prediabetic db/db mice.