Treatment with direct moxibustion led to a marked improvement in CIA and atrophy of individual muscle fibers. Collagen protein signaling in the muscle of the CIA group was stronger than the control and CIA + moxi groups. Myostatin protein expression, as determined by Western blotting and immunofluorescent staining, were stronger in the CIA group compared with the control and CIA + moxi groups. Immunofluorescent staining confirmed that the CIA group had the strongest TGF-B1 protein signals among the three groups. However, in serum analysis the intact control group showed the strongest TGF-B1 protein signaling. RT-PCR analysis of the muscle tissues of the CIA + moxi group showed significant IGF-1 mRNA expression, and the most intense phospho-Erk1/2 protein signaling was detected in the muscle tissues of the CIA group via Western blotting and immunofluorescent staining. These results confirm that the direct administration of moxibustion at Shenshu (BL 23) and Zusanli (ST 36) influences muscle regeneration in the CIA mouse model. Our results suggest that the establishment of the moxibustion mechanism will encourage the clinical application of moxi.