To observe the effect of moxibustion on the expressions of tumor necrosis factor-α (TNF-α) and nuclear transcription factor kappa B (NF-κB) proteins in ankle joints of rats with rheumatoid arthritis (RA), and to explore the anti-inflammatory mechanism of moxibustion in the treatment of RA. Adjuvant arthritis (AA) rat models were induced and used as rat models of RA. Rats were randomly divided into a normal group, a model group, a moxibustion group and a saline group. Rats in the normal and model groups were not treated; rats in the moxibustion group accepted treatment by moxibustion at Zusanli (ST 36) and Shenshu (BL 23) after modeling; rats in the saline group were injected with 0.15 mL saline to the bottom of the left hind paw and had no other treatments. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of rats’ ankle joints under light microscope. Immunohistochemistry was used to observe the expressions of TNF-α and NF-κB in ankle joints of rats. Compared with the normal group, the rats’ ankle joints in the model group showed disorganization, joint surface defect, and significantly increased mean optical density (MOD) of TNF-α and NF-κB (all P