Objective: To observe the regulatory effects of herbal cake-partitioned moxibustion on Crohn's disease (CD) rat’s colon inflammatory cytokine interleukin-17 (IL-17), IL-23 and their mRNAs, and to investigate the action mechanism of moxibustion in treating CD. Methods: Forty SPF grade Sprague-Dauley (SD) male rats were randomly divided into a normal group, a model group, an herbal cake-partitioned moxibustion group and a Western medicine group, with 10 rats in each group. Except the normal group, rats in the other three groups were used to make CD model by giving an enema in colon with Trinitro-benzene-sulfonic acid (TNBS). When the models were successful made, rats in the model group had no therapeutic intervention; rats in the herbal cake-partitioned moxibustion group were subjected to herbal cake-partitioned moxibustion treatment at bilateral Tianshu (ST 25) plus Qihai (CV 6); and rats in the Western medicine group were given oral Mesalazine. After treatment, the histopathological changes and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were observed in descending colon by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) methods. Results: Colon tissues of TNBS enema rat models showed cracks-like ulcers accompanied by mucous layer inflammation, granulomas, and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all higher than those in the normal group (P<0.01); after intervention, colon tissue cracks-like ulcers and inflammation degree reduced, inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all significantly decreased (P<0.01) in the herbal cake-partitioned moxibustion group and the Western medicine group. Conclusion: Herbal cake-partitioned moxibustion may improve colon tissue ulcers and relieve intestinal inflammation by down-regulation of IL-17, IL-23 and their mRNAs expressions in CD model rats’ colonic mucosa. © 2016, Shanghai Research Institute of Acupuncture and Meridian and Springer-Verlag Berlin Heidelberg.