This study aimed to elucidate possible age-related changes in islet blood perfusion in lean and obese C57BL/6 mice. Obese mice aged 1 mo were hyperglycemic and hyperinsulinemic and had an increased islet blood flow compared with age-matched lean mice. This augmented blood flow could be abolished by pretreatment with leptin. The islet blood perfusion was, in contrast to this, markedly decreased in obese 6- to 7-mo-old animals compared with age-matched lean mice. Reversal of hyperglycemia, but not hyperinsulinemia, in these obese mice with phlorizin normalized the islet blood flow. Spontaneous reversal of hyperglycemia, but not hyperinsulinemia, was seen in the 12-mo-old obese mice. Islet blood perfusion in obese mice at this age did not differ compared with lean mice. It is suggested that the initial increase in islet blood flow in obese mice is due to the leptin deficiency. The subsequent decrease in islet blood perfusion is probably caused by the chronic hyperglycemia. The described islet blood flow changes may be of importance for impairment of islet function in obese-hyperglycemic mice.