Aim To investigate the immunomodulatory effects of sea cucumber fucoidan ( SC-FUC) on macro-phage and the signaling pathways. Methods Cell via-bilities in response to different concentrations of SC-FUC were analyzed by MTT, phagocytosis ability was detected by neutral red,and nitric oxide ( NO) produc-tion was examined by Griess reaction kit. The mRNA expression levels of IL-6 , IL-10 , Toll-like receptors (TLRs) and related signal molecules MyD88, TRIF, NF-κB were assayed by real-time PCR. All the experi-ments were based on murine RAW264. 7 cell line. Re-sults SC-FUC could promote RAW264 . 7 cell prolif-eration, phagocytosis as evidenced by uptake of neutral red and release of NO. The effects were significant at the early stage (6 h and 12 h) . SC-FUC could up-reg-ulate the expression of IL-6 , IL-10 , TLR4 , TLR5 , TLR9. Moreover, mRNA expressions of TLRs signaling molecules were increased, as well as MyD88, TRIF, NF-κB. Conclusions SC-FUC could activate macro-phage, and then promote the immune function by pro-moting production or expression of NO, IL-6, IL-10. It is speculated to be relevant to activated cell surface re-ceptors in macrophage, including TLR4, TLR5, TLR9, and NF-κB signaling pathways.