Kupffer cell imaging is a powerful tool for the detection of liver cancer. This diagnostic procedure depends on the faculty of the reticuloendothelial system (RES) which takes up foreign bodies, including small particles. The current study aimed to develop a novel RES targeting liposomal contrast agent that functionalized with serine or mannose, the moiety specifically binding to a corresponding receptor on phagocytic cells. Liposomes loaded with non-ionic X-ray contrast media, Iohexol, were prepared by supercritical carbon dioxide reverse-phase evaporation method and were intravenously injected to healthy rabbits in order to evaluate the liver parenchymal enhancement in X-ray computed tomography (CT). From 10 to 40 min after injection, the mean enhancement value of the liver parenchyma approached 45 and 34 Hounsfield units (HU) when serine-modified iodinated liposomal contrast agent (ILCA) and mannose-modified ILCA were applied, respectively. The tumor-to-liver contrast values were also evaluated after the administration of the prepared ILCA to rabbits with VX-2 carcinoma. For serine-modified ILCA, tumor-to-liver contrast was 82 HU at 1 min and >24 HU at 10-40 min; for mannose-modified ILCA, the values were 58 HU at 0.5 min and >21 HU at 10-40 min. These vales estimated from the region of intrest and the imaging figures of liver indicate the potential of ILCA for clinical use.