This study observed the changes in the blood nerve barrier (BNB) in rat chronic neuropathic pain and investigated the role of tight junction protein Claudin-1 in regulating it’s permeability. Methods: Healthy female SD rats were randomly divided into the control group, sham operation group (sham group), and chronic constriction injury of sciatic nerve group (CCI group). No treatment was given in the control group; the right sciatic nerves of rats were exposed but not ligated in the sham group; the sciatic nerves were separated and treated with four loose knots in the CCI group. The change in sciatic nerve permeability was observed by studying Evans blue-labelled albumin (EBA). The distribution of Claudin-1 in the sciatic nerve was detected by immunofluorescence staining. The right hindlimb mechanical pain threshold was measured at 6 h, 1 d, 7 d, and 14 d after operation. The transcription levels of Claudin-1 mRNA were detected by RT-PCR, and the expression levels of Claudin-1 protein were determined by Western blot. Results: Compared with the control group and sham group, the CCI group showed significantly decreased hindlimb mechanical pain thresholds beginning 1 d after operation, reaching its lowest point at 7 d, and maintaining this level until 14 d (all P<0.05). The CCI group showed significantly increased EBA penetration 1 d after operation (P<0.05). Compared with the other two groups, the CCI group showed a significant decrease in Claudin-1 mRNA transcription levels and Claudin-1 protein expression levels in the sciatic nerve at 6 h, 1 d, 7 d, and 14 d after operation (all P<0.05). Immunofluorescence staining of the sciatic nerve showed that Claudin-1 was mainly distributed within the endoneurium and perineurium. Compared with the other two groups, the CCI group displayed significantly reduced intensity in Claudin-1 protein fluorescence within the sciatic nerve perineurium 1d after operation (both P<0.05). Conclusion: In rats with chronic neuropathic pain, the expression level of Claudin-1 protein is reduced, resulting in the destruction of the BNB in the sciatic nerve.