Objective To explore the mechanism of transforming growth factor β1 (TGFβ1)/Smad3 signaling pathway in parecoxib in relieving neuropathic pain in rats. Methods Forty SD rats were randomly divided into sham operation group (SC group), neuropathic pain group (CCI group), parecoxib group (PAR group), parecoxib+TGFβ1 inhibitor 1D11 group (1D11 group) (n=10). A rat model of neuropathic pain was constructed by chronic sciatic nerve constriction injury. After modeling, the PAR group was given 10 mg/kg parecoxib intraperitoneally for 7 consecutive days. The 1D11 group was given 10 mg/kg parecoxib and 1 mg/kg 1D11 intraperitoneally for 7 consecutive days. At 1d before surgery, 3, 7, and 14 days after surgery. The mechanical pain threshold and thermal pain threshold were measured. Western blot was used to detect the expression of TGFβ1/Smad3 signaling pathway. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1 (Iba-1) protein. Real-time quantitative PCR was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).Results Compared with CCI group, the mechanical pain threshold and thermal pain threshold in par group increased at 3D, 7d and 14d after operation, and TGF in spinal dorsal horn tissue increased β 1. The expression level of P Smad3 increased, the fluorescence intensity of IBA 1 decreased significantly, and IL 1 β, IL-6, TNF- α The level decreased, and the difference was statistically significant (P<0.05). 1d11 can inhibit the above protective effects of parecoxib sodium to varying degrees.Conclusion Parecoxib can alleviate neuropathic pain, inhibit the activation of microglia and reduce the expression of inflammatory factors. This therapeutic effect may be related to the activation of TGFβ1/Smad3 signaling pathway, which provides a new theoretical basis for the clinical treatment of parecoxib.