Background: Lactobacillus plantarum (LP) 06CC2, isolated from Mongolian traditional food, affects the systemic immune activity of NK cells. Here, we investigated the beneficial anti-colitis effect of LP 06CC2 in dextran sulphate sodium (DSS)-induced colitis in C57BL/6 mice. Methods: Mice treated with 1% DSS were administered PBS only (control group) or heat-killed lyophilised LP 06CC2 (LP group) by oral gavage for 19 consecutive days. We assessed the severity of colitis using a disease activity index, measured colon length and weight, and examined colon tissue macroscopically and histopathologically. We also collected colonic lamina propria mononuclear cells (LPMCs), in which we monitored expression of genes encoding inflammatory cytokines (IFN-γ, IL-6, IL-12, TNF-α, and IL-10). To further characterise the involvement of IL-10 in the effects of LP06CC2, we continuously administered neutralising anti–IL-10 monoclonal antibody to mice with DSS-induced colitis, with or without LP 06CC2 feeding. Results: Reduction in body weight, disease activity index, and pathology score were all significantly lower in the LP group than in the control group (p<0.05). The LP strain prevented shortening of the large intestine: average colon length was significantly shorter in the LP group than in the control group (p<0.01). IL-10 expression in CD11c-positive cells in colonic LPMCs was significantly higher in the LP group than in the control group, although there was no significant difference in expression of IFN-γ or IL-12 between the groups. After administration of anti–IL-10 neutralising antibody, the reduction in body weight in the LP group was the same as that in the control group. Thus, the positive effects of LP, i.e., prevention of body weight loss following administration of DSS, were abolished by neutralisation of IL-10. Conclusions: LP 06CC2 attenuated colon inflammation by inducing IL-10 production in colonic dendritic cells.