Circadian clocks are located in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in the peripheral tissues of mammals. Recent molecular studies have revealed that the phase of circadian gene expressions in peripheral clocks could entrain to time-imposed restricted feeding (RF) independently of the SCN. To elucidate whether endogenous insulin is involved in the entraining mechanisms of peripheral clocks to RF, we examined the expression profiles of clock genes in peripheral tissues of mice with diabetes induced by streptozotocin (STZ). The circadian expressing genes (mPer1, mPer2, and BMAL1) underwent a phase-shift induced by RF in the heart, liver, and kidney of both diabetic and normal animals. However, the expression phase of mPer1 in these tissues of the diabetic mice. significantly differed from those in the normal animals under RF. The expression phase of the circadian output gene, albumin D-site binding protein (DBP), was completely shifted by RF both in normal and in diabetic mice, suggesting that the endogenous insulin is not essential for the entrainment of peripheral clocks to feeding cycles in mice. (C) 2004 Elsevier Inc. All rights reserved.