Cytokine production by Kupffer cells, which is regulated by NFκB, causes severe liver injury in endotoxin syndrome. NFκB decoy has been reported to inhibit NFκB-mediated transcription. The purpose of this study is to inhibit LPS-induced cytokine production by Kupffer cell-targeted delivery of NFκB decoy using fucosylated cationic liposomes (Fuc-liposomes). Cholesten-5-yloxy-N-{4-[(1-imino-2-l-thiofucosyl-ethyl)-amino] butyl-}formamide (Fuc-C4-Chol) was synthesized to prepare Fuc-liposomes. Tissue accumulation, intrahepatic distribution and serum cytokine concentrations were investigated after intravenous injection of Fuc-liposomes/NFκB decoy complexes. Intravenously injected Fuc-liposome complexes rapidly and highly accumulated in the liver while little naked NFκB decoy accumulated in the liver. An intrahepatic distribution study showed that Fuc-liposome complexes are mainly taken up by non-parenchymal cells. The liver accumulation of Fuc-liposome complexes was inhibited by GdCl 3 pretreatment, which selectively inhibited Kupffer cell uptake. This result suggested that Kupffer cells contribute to liver accumulation. TNFα, IFNγ, ALT and AST serum levels in LPS-infected mice were significantly attenuated by treatment with Fuc-liposome complexes compared with naked NFκB decoy. Fuc-liposome complexes also reduced the amount of activated NFκB in the liver nuclei. Fuc-liposomes would be a useful carrier for Kupffer cell-selective delivery of NFκB decoy by intravenous injection.