Objective To observe influence of moxibustion at "Shenshu" (肾俞BL 23) and "Zusanli" (足三里 ST 36) on proteins expression of Ras, ERKI/2, and Raf in synovial tissues in rats with rheumatoid arthritis (RA) to elucidate molecular mechanisms of moxibustion on treating RA. Methods Thirty Wistar rats were randomly divided into a normal control group (Group Cont), a model group (Group Mod) and a moxibustion group (Group Mox) with 10 rats in each group. The model was established by using both environmental factors such as wind, cold and damp and a biological factor (Freund's complete adjuvant). Suspended moxibustion was applied at bilateral BL 23 and ST 36 for 20 min, applied once daily for 15 days, starting from the 3rd day after modeling. Volumes of metaleg digiti pedis on the right side were measured before, after and 15 days after modeling. Protein expressions of Ras, ERK 1/2, p-ERKI/2 and Raf in synovium tissues were detected by western blot. Results After modeling, volumes of metaleg digiti pedis on the right side were significantly enlarged, compared with those of rats in Group Cont (P〈0.01). After treatment by moxibustion for 15 days, the metatarsale girth of metaleg digiti pedis on the right side in Group Mox was significantly reduced, compared with that in Group Mod (P〈0.01). Protein expressions of Ras, Raf, ERK1/2 and p-ERK1/2 in Group Mod were significantly increased, compared with those in Group Cont (P〈0.01) and Group Mox (P〈0.01). Protein expressions of Ras, Raf, ERK1/2 and p-ERK1/2 in Group Mox were significantly lowered, compared with those in Group Mod (all P〈0.01). Conclusions Moxibustion can suppress excessive protein expressions of Ras, Raf and ERK1/2 in synovium tissues of rats with experimental RA to inhibit abnormal activation of Ras-MAPK signal Pathway, which may be one of the molecular mechanisms of moxibustion in alleviating synovitis.