Abstract: Colitis is an inflammatory bowel disease with relapsing properties and the incidence has been increased in recent decades. More and more studies show that probiotics can be used to alleviate colitis. In this study, a mouse model of colitis induced by dextran sulfate sodium (DSS) was constructed to explore the alleviating effect of Lactobacillus plantarum 1201 on DSS-induced colitis. The experimental mice were divided into normal group, model group and 1201 group. Colitis was induced in the other groups except the normal group. At the same time, mice in the 1201 group were given 0.2 mL of 1×10⁹ CFU/mL L. plantarum 1201 by gavage daily for 12 days. Then, the colon morphology of mice was observed by H&E staining, the fecal albumin content of mice was detected, and the mRNA level of NF-κB, inflammatory factors (TNF-α, IL-6, IL-22, IFN-γ, IL-17A, TGF-β1) and tight junction proteins (ZO-1, Ocludin and Claudin-3) in colon were detected by fluorescence quantitative PCR technology. In addition, 16S rRNA high sequencing technology was used to detect the changes of intestinal flora in mice, and metabolomics was used to analyze the changes of intestinal metabolites. The results showed that L. plantarum 1201 increased the relative abundance of Bifidobacterium, Lactobacillus and Akkermansia, reduced the relative abundance of Escherichia, and reduced the ratio of Firmicutes/Bacteroidetes, to improve the balance of intestinal flora. Meanwhile, L. plantarum 1201 also inhibited NF-κB and the inflammatory factors (TNF-α, IL-6, IL-22, IFN-γ). In addition, it increased the mRNA expression of colon tight junction proteins (ZO-1, Ocludin and Claudin-3) and the serum level of beneficial metabolites, including α-Tocopherol and L-Fucose. In conclusion, the results show that L. plantarum 1201 has the potential to alleviate colitis.