In the last years, only few studies focused on the role of tight junctions in human peripheral nerve. This type of junction is found between apposed membranes of myelinating Schwann cells, between perineurial cells and between endothelial cells (of the epi-, peri- and endo-neurium vessels). We investigated the presence of claudin-1 and occludin in peripheral nerve biopsy of patients with demyelinating peripheral neuropathies by immunolabeling (immunohistochemistry and immunofluorescence) and Western blot. Immunolabeling highlighted claudin-1 expression mostly in the tight junctions of the perineurial cells and in the autotypic junctions of the Schwann cells of the patients with demyelinating peripheral neuropathies. Occludin was mostly expressed in the tight junctions of perineurial cells and endothelial cells and only faintly in autotypic junctions of Schwann cells. The Western blot data showed significant differences in claudin-1 and occludin expression levels in patients with demyelinating peripheral neuropathies versus normal unaffected control. Our results show that autotypic tight junctions molecular composition, like claudin-1 and occludin expression could influence the demyelinating process by altering the permeability of the blood-nerve barrier.