Abstract: Objective To study the effect of zinc on expression of substance P in mice with sciatic nerve injury (SNI). Methods Forty-eight CD1 mice were divided into control group, neuropathic pain (NPP) group, low NPP (L- NPP) group, and high NPP (H- NPP) group.A NPP model of mice was induced by surgery for SNI. Mice in control group underwent sham operation (isolating sciatic nerve)while those in N-NPP group, L- NPP group and H- NPP group underwent surgery for SNI after they were fed with forage containing zinc at the dose of 30 mg/(kg·d) and 0.85 mg/(kg·d) and with zinc sulfate water solution at the concentration of 227 mg/(L·d)respectively for 2 weeks. Effect of zinc on expression of substance P in mice with SNI was detected by atomic absorption spectrum，immunohistochemistry, immune blotting and image analysis respectively on day 7 after operation. Results The serum zinc level in spinal cord was significantly higher and the substance P expression level was significantly lower in H-NPP group than in L-NPP group (P＜ 0.01). Conclusion Zinc can inhibit the expression of substance P in mice with SNI.