Thiocolchicine is a colchicine-derivative used in the therapy of some diseases and extensively studied in the field of oncological research as antimitotic agent. Here we studied the activity of thiocolchicine on the cytoskeleton of the peroneus nerve, performing a histological and ultrastructural analysis. We observed a decrease in mean myelinated fiber area in thiocolchicine-treated rats in comparison to controls; this was due to a decrease in mean axoplasm area, while myelin thickness was constant. In the ultrastructural analysis a decrease in microtubule density and an increase in neurofilaments were found; moreover, the myelinated fibers seemed to be more affected in comparison to the unmyelinated axons. These findings are in agreement with the capability of binding to microtubule skeleton shared by all the colchicinoids.