This study observed the inhibitory effect of Lactobacillus plantarum YS-4 (LP-YS4) on the colitis through mice colitis which was induced by DDS (Dextran Sulfate Sodium). By observing the colon shape of mice, the test kit and quantitative PCR (polymerase chain reaction) technique were used to detect the mice, and the effect of LP-YS4 was compared with the positive control of drug sulfasalazine. The results showed that LP-YS4 can increase the colon length of colitis mice and improve the ratio of colon weight/ colon length. The tests on serum of mice showed that LP-YS4 could reduce Endothelin (ET), Substance P (SP), Interleukin-10 (IL-10) levels and increase Somatostatin (SS), Vasoactive Intestinal Peptide (VIP), Interleukin-2 (IL-2) levels in serum of colitis mice. The tests on colon tissue in mice showed that LP-YS4 could improve Glutathione (GSH), Superoxide Dismutase (SOD) activities and decrease Myeloperoxidase (MPO), Malonaldehyde (MDA) activities in the colon of colitis mice; and LP-YS4 could also increase the expression of neuronal Nitric Oxide Synthase (nNOS), endothelial Nitric Oxide Synthase (eNOS), c-Kit, Stem Cell Factor (SCF) mRNA and decrease the expression of inducible Nitric Oxide Synthase (iNOS), Interleukin-8 (IL-8), Chemokine (C-X-C motif) Receptor 2 (CXCR2) in the colon of colitis mice. It can be seen that LP-YS4 has the effect of colitis suppression, the effect of high concentration LP-YS4 is close to the drug sulfasalazine.