Intestinal fibrosis is the main pathological process in Crohn's disease (CD); acupuncture and moxibustion can inhibit the process of fibrosis in CD rats, but the regulatory mechanism remains unknown. The present study observed the effect of moxibustion on the extracellular signal-regulated kinase (ERK) signaling pathway in the CD rat. The result shows that the phosphorylation of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and the expression of the corresponding mRNAs in the colon tissue of CD rat were significantly higher than the normal control group. Both treatments with mild moxibustion and with herb-separated moxibustion significantly reduced the expression of the Ras, Raf-1, MEK-1, and ERK-1/2 proteins and Ras and Raf-1 mRNA. MEK-1 and ERK-1/2 mRNA expression in each treatment group showed a downward trend, and the ERK-1/2 mRNA levels were significantly lower in the mild moxibustion group. It indicates that Ras, Raf-1, MEK-1, and ERK-1/2 are involved in the process of intestinal fibrosis in CD rats. Moxibustion can downregulate the abnormal expression of colonic Ras, Raf-1, MEK-1, and ERK-1/2 protein and mRNA levels in CD intestinal fibrosis in rats. Moxibustion may play a role in the treatment of CD intestinal fibrosis by regulating ERK signaling pathway.