Annexin II (AX II) is a member of the family of calcium-dependent actin- and phospholipid-binding proteins implicated in numerous intracellular functions such as signal transduction, membrane trafficking, and mRNA transport, as well as in the regulation of membrane/cytoskeleton contacts and extracellular functions. AX II is expressed in the central nervous system (CNS) and is upregulated in some pathological conditions. However, expression and localization of this protein in the peripheral nervous system (PNS) is still uncertain. In the present study, we examined the expression and distribution of AX II in the PNS. By western blot analysis, we found that a higher level of AX II was present in sciatic nerve homogenates than in brain homogenates. RT-PCR of total RNA from rat sciatic nerves revealed that AX II was synthesized within the nerves. Immunohistological analysis showed the characteristic distribution of AX II in Schmidt–Lanterman incisures (SLI) as well as in the paranodal regions. Localization of AX II in the PNS was examined in two mutant mouse models, shiverer and cerebroside sulfotransferase knockout mice, both of which show increased numbers of SLI. The paranodal axo-glial junction is also disrupted in the latter. Interestingly, the staining intensities of AX II in these regions were increased markedly in both mutants, suggesting that not only the numbers but also AX II content in each incisure and paranodal loop were affected. From its characteristic distribution and molecular features, AX II may be important for myelin function in the PNS. © 2007 Wiley-Liss, Inc.