Abstract Recently, the incidence of Inflammatory Bowel Disease (IBD) is increasing due to westernized lifestyle and eating habits. IBD is a representative gastrointestinal immune disease, and casued by an excessive immune response in the gastrointestinal tract. In recent studies, lactic acid bacteria which known as beneficial intestinal microbiota have protective effects on IBD by various mechanisms. Here, we evaluated the protective effect of Lactobacillus sakei CVL-001 isolated from korean tradtional food kimchi against dextran sulfate sodium-induced colitis in mice. First, administration of Heat-killed (HK) CVL-001 showed protective effects against DSS-induced colitis. Also, colonic mRNA expression levels showed that pro-inflammatory cytokine was downlregulated and anti-inflammatory cytokine was upregulated. Nucleotide-oligomerization domain 2 (NOD2) is well known as innate immune receptor and deeply related to IBD. We found that HK CVL-001 induced a NOD2-dependent regulatory phenotype in mouse bone marrow derived dendritic cell (BMDCs). Especially, we demonstrated that the expression of CD103, which is known as a marker of tolerogenic DC, was expressed mediated by NOD2. In vivo studies, colon administered with HK CVL-001 favoured the expansion of mucosal CD103 DCs and regulatory T cells. However, protective effect was abolished in NOD2 knockout mice. This results indicated that Heat killed L. sakei CVL-001 might be used therapeutic agent and strategy in IBD. This research was supported by the Mid-Career Researcher Programs (Grant No. 2022R1A2C2012287) of the National Research Foundation of Korea funded by the Ministry of Science and ICT (Information and Communication Technologies).