In order to study polysaccharides of lettuce stem, lettuce stem was used as materials to prepare water soluble polysaccharides with the method of water extraction-alcohol precipitation. Monosaccharide components and immunomodulatory activities of polysaccharides were measured by using HPLC and administration route of RAW 264.7 macrophage cells. The results demonstrated that lettuce stem polysaccharides were mainly composed of galacturonic acid, galatose and arabinose in a mole ratio of 22.6030.4217.88. In the range of 5～200 μg/mL of test concentrations, lettuce stem polysaccharides significantly promoted the proliferation, phagocytosis and NO product of RAW264.7 macrophage cells, which suggested that lettuce stem polysaccharides had a immunomodulatory activity. All the results provided a theory evidence for high utilization and product development of lettuce stem.