The biodistribution of liposomes modified by mannobiose residues was studied in rat. The purpose of the modification was to target the liposomes to macrophages. Mannobiose mono arachidic acid esters (MAEs) were synthesized and used to modify the surface of liposomes. It was shown by gel permeation chromatography that the MAE was preferentially incorporated into the membrane of the liposomes. After intraveneous administration, mannobiose-modified lisposomes were eliminated from the systemic circulation more rapidly than control liposomes without the modification. Whilst the modification did not affect the distribution of liposomes to kidney, lung, or thymus, it increased the distribution to liver and spleen. The uptake in the hepatic parenchymal cell fraction was not influenced by MAE incorporation. Taking into account the fact that endothelial cells do not take up particles whose size is > 100 nm, the increase in the distribution to liver were ascribed to an increase in uptake by Kupffer cells. These results suggest that mannobiose mono fatty acid esters are useful in the targeting of liposomes to Kupffer cells and other macrophages.