To observe the effects of acupuncture and moxibustion on DNA methyltransferase in the colon tissues of rats with Crohn's disease (CD) and explore the mechanism of acupuncture and moxibustion in the epigenetic regulation of CD.Methods:SD rats were randomly divided into a normal group，a model group，an indirect moxibustion group，an electroacupuncture (EA) group，and a sulfasalazine group.The CD model was induced by enema with 5% 2,4,6-trinitrobenzene sulfonic acid in rats.The rats in the indirect moxibustion group and the EA group were treated correspondingly at bilateral “Tianshu” (ST 25) and “Qihai” (CV 6)，and those in the sulfasalazine group received sulfasalazine enteric-coated tablets by gavage.ELISA was used to detect the protein content of CRP，IL-6，IL-1β，and TNF-α in the serum.RT-qPCR was used to detect the expression of HIF-1α mRNA in the colon tissues.Western Blotting was used to detect the protein expression of DNMT1，DNMT3a，and DNMT3b in the colon tissues.Results:Compared with the normal group，the model group showed increased protein content of CRP，IL-6，IL-1β，and TNF-α in the serum (P<0.01).Compared with the model group，the indirect moxibustion group，the EA group，and the sulfasalazine group showed decreased protein content of the above-mentioned inflammatory factors (P<0.01).Compared with the normal group，the model group displayed increased expression of HIF-1α mRNA and DNMT1，DNMT3a，and DNMT3b proteins in the colon tissues (P<0.01).Compared with the model group，the indirect moxibustion group and the sulfasalazine group exhibited decreased expression of HIF-1α mRNA and DNMT1，DNMT3a，and DNMT3b proteins (P<0.05 or P<0.01)，and the EA group showed reduced expression of HIF-1α mRNA and DNMT1 protein (P<0.05 or P<0.01).Conclusion:The indirect moxibustion and EA can both inhibit the expression of inflammatory factors such as CRP，IL-6，IL-1β，TNF-α，as well as HIF-1α and DNMT1 in CD rats，and the indirect moxibustion can also inhibit the expression of DNMT3a and DNMT3b，which may be one of the mechanisms of acupuncture and moxibustion in reducing intestinal inflammation in CD.