Objective To explore the effects of the changes in location and quantity of splenic dendritic cells (DCs) on the peripheral immune organ injuries of mice with multiple organ dysfunction syndrome (MODS). Methods The MODS model of C57BL/6 mouse was established by zymosan intraperitoneal injection. Fifty mice were randomly divided into groups of control, 3-6 hours, 12-48 hours, 5-7 days and 10-12 days post trauma (10 each). The number of splenic DCs (CD11c high+ ) was counted by flow cytometry, and the location and migration of splenic DCs (CD11c+) were studied by immunohistochemistry labelling. Results In the control group, splenic CD11c+ DCs were only about 1.62% of all spleen mononuclear cells and mainly located at the margin between the splenic red pulp and white pulp. In the 3-6h group, number of splenic CD11c+ DCs (2.62%) was more than that in control group (P0.01), and the cells mainly located in the T cell area and less in the marginal area of the spleen. In the 24-48h group, number of splenic CD11c+ DCs (1.40%) was less than that in 3-6h group (P0.01) and no statistical difference compared with that in control group (P0.05), and mainly located in the T cell area. In the 5-7d group, splenic CD11c+ DCs (1.45%) decreased to the level of control group, and located both in the marginal zone and T cell area. In the 10-12d group, number of splenic CD11c+ DCs (1.79%) was more than that in control group (P0.05), and mainly located in the margin zone. Conclusions In the early stage (the prior 48h) of MODS, splenic DCs increase markedly and migrate from the margin zone into the T cells areas, inducing excessive immunoreactions; while in the late stage (10-12d), splenic DCs stay in the marginal zone and thereby less contact with T cells, which might participate in the immunosuppression and pathogenesis of MODS. The location and quantity of splenic DCs may play an important role in the immune disorder and pathogenesis of MODS.