To investigate the reversibility of the neuropathy induced by 2,5-HD, adult male rats were administered at a dosage of 400 mg/kg/day 2,5-HD (five times per week) for 2, 4, and 8 weeks, respectively. After stopping HD exposure, half of 8-week treated animals were allowed to naturally recover for 16 weeks. The relative levels of NF-H, NF-M, and NF-L in spinal cords and sciatic nerves of rats were determined by immunoblotting during the HD neuropathy. The results showed that NFs content in nerve tissues demonstrated a progressive decline as the intoxication continued. Furthermore, after a recovery of 16 weeks, the levels of three NF subunits in spinal cords of treated rats returned to normal while those in sciatic nerves displayed an inconsistent reversal. Among them, the level of NF-H in sciatic nerves returned to normal completely, and NF-L also showed a significant improvement, whereas NF-M did not demonstrate an obvious reversal. These findings suggest that HD-induced NFs decline is at least partially irreversible within the time frame of this study, which might be associated with the incomplete recovery of neurological dysfunctions of HD-treated rats.