Young male Zucker rats with a leptin receptor mutation are obese, have a non-insulin-dependent diabetes mellitus (NIDDM), and other endocrinopathies. Fine structure aspects of the tibial branches of the sciatic nerve of lean (Fa/?) and obese (fa/fa) perfused rats were compared and revealed a progressive demyelination caused by Schwann cells (SCs). There, stacked myelin layers membranes and other adhering junctions were defective in many nerve fibers of the obese rats, including of the mesaxons of the smallest fibers. Additionally, the progressive myelin alterations caused by metabolomic alterations in membrane components sorted by the SCs may also have revealed a peculiar, centripetal mode of sorting and trafficking maintenance of the peripheral nerve myelin.