Background: Alginate materials have been widely employed for biomedical applications ranging from wound healing to cancer treatment. However, how alginate materials affect the immune system is largely unknown. Objective: To explore the impact of alginate materials on immune system. Methods: The effect of three types of alginate materials, low viscosity, high viscosity and particulate alginate, were examined by both in vivo and in vitro analyses. C57BL/6J (B6) mice were treated with alginate and peripheral blood was tested by ELISA for cytokine production. Dendritic cells, macrophages and splenocytes isolated from mice were analyzed for the response to alginate treatment. Administration of alginates by intra lymph node injection (I.L.N.) yielded more potent cytokines productions than other injection routes. Results: Alginate materials did not affect the viability of lymphocytes. Particulate alginate induced the most potent inflammatory reaction as determined by the production of cytokines, such as, IL-1β, IL-8, TNF-α and IFN-γ. Low viscosity and particulate alginates are more effective than high viscosity alginates in activating dendritic cells as indicated by the expression of dendritic cells surface markers (CD80, CD86 and CD40). Similarly, the level of G-CSF was slightly higher in particulate alginate treated macrophages. Conclusion: Alginate materials could affect immune response through different ways, including promoting inflammatory cytokine production, and activating dendritic cells. Therefore, alginate materials, especially in particulate form, have the potential to be applied in inflammation related diseases.