This study investigates the comparative anatomy of peripheral nerves across five species—human, rat, mouse, monkey, and dog—to understand how structural variations influence neuropathy susceptibility. Utilizing advanced histological techniques and imaging, we measured the thickness of axons, myelin sheaths, endoneurium, perineurium, and epineurium in nerve tissue samples from each species. Our analysis revealed significant differences: monkeys and humans generally had thicker axons and myelin sheaths compared to rats and mice. These structural differences corresponded with varying incidences of neuropathies, with rats showing higher rates of chemotherapy-induced neuropathies and monkeys exhibiting a different neuropathic profile. Advanced imaging techniques provided more detailed insights into nerve structure, supporting our hypothesis that structural variations impact neuropathy susceptibility. The study highlights the importance of considering anatomical differences when selecting animal models for research and developing targeted therapies. By addressing gaps in comparative nerve anatomy, these findings contribute to a deeper understanding of peripheral nerve function and potential therapeutic strategies.