Crohn's disease (CD) is a major subtype of inflammatory bowel disease (IBD). Herb-partitioned moxibustion (HPM) has been proven to be effective in treating CD by a large amount of clinical and experimental researches. MiRNAs (microRNAs) are increasingly recognized as important posttranscriptional regulators of inflammatory genes. In this study, we established experimental CD rat models and investigated the miRNAs associated with the onset of experimental CD; then, we further identified CD-related miRNAs that were regulated by HPM and explored the relationship between CD and the potential target genes of involved miRNAs. We found that miR-147 and miR-205 were significantly downregulated in colons of experimental CD rats and may be closely associated with the onset of experimental CD. HPM may extenuate inflammatory responses in colons and ameliorate colonic damages in CD via upregulating the expression of miR-147 and miR-205 and then further downregulating the expression of inflammation-related mRNAs, negatively regulating inflammatory signal pathways, and reducing the production of downstream inflammatory cytokines.