Objective To investigate the effect of Heiguteng Zhuifenghuoluo Capsule (HZC) on nuclear factor kappa B (NF-κB)-related protein in rheumatoid arthritis rats, and to analyze the expression of IκBα, NF-κBp65, phospho-nuclear factor kappa B p65 (p-NF-κBp65), receptor activator of nuclear factor κB ligand (RANKL), transforming growth factor activated kinase 1(TAK1), transforming growth factor β activated kinase binding protein 1(TAB1), monocyte chemoattractant protein 1 (MCP-1), C-X-C motif chemokine ligand 1 (CXCL1), macrophage inflammatory protein-1 (MIP-1) of plasma in rheumatoid arthritis rats. Methods Male SD rats were randomly divided into control group, model group, HZC (0.315 g/kg) group, and HZC (0.315 g/kg) plus ammonium pyrrolidinedithiocarbamate (PDTC, 0.01 g/kg) group. The model was constructed in all groups except the control group. Five weeks after modeling, the plantar thickness and spleen organ coefficient (spleen/body weight ratio) were measured in all rats. The TAK1 and TAB1 proteins were detected by immunohistochemical method in the spleen. Western blot analysis was used to detect the expression of IκBα, NF-κBp65, p-NF-κBp65 and RANKL proteins in the synovium of joint and plantar tissue. MCP-1, CXCL1, MIP-1 expression in the plasma was detected by ELISA. Results Compared with the model group, the swelling degree of plantar and the spleen organ coefficient in the control group, HZC group and combined administration group decreased significantly. The immunohistochemistry showed that the expression of TAK1 and TAB1 proteins in the spleen were down-regulated in the control group, HZC group and combined administration group. Western blotting showed that the expression of IκBα protein was up-regulated in the synovium of joint tissue of the control group, HZC group and combined administration group, but the expression of NF-κBp65, p-NF-κBp65, RANKL proteins were down-regulated in the control group, HZC group and combined administration group. ELISA showed that the expression of plasma MCP-1, CXCL1, MIP-1 were down-regulated in the control group, HZC group and combined administration group. Conclusion HZC inhibits the inflammatory response of rheumatoid arthritis rats by regulating NF-κB-related proteins.