Lycopene existing in tomato is a nonprovitamin carotenoid with potent antioxidant properties. In addition to the antioxidant activities, lycopene is know to show anti-inflammatory effects through the inhibition of secretion of proinflammatory agents such as nitric oxide (NO) and cytokines from stimulated immune competent cells. In this study, we investigated the effects of lycopene on the secretion of NO and tumor necrosis factor-α (TNF-α) from mouse macrophage cell line RAW264.7 cells stimulated with CEL-I, a GalNAc-specific C-type lectin isolated from marine invertebrate Holothuroidea (Cucumaria echinata). Lycopene at 10μM showed significant inhibitory effect on the secretion of NO from CEL-I-stimulated RAW264.7 cells, and more potent inhibitory effects on NO and TNF-α secretions were observed at 100μM. Fluorescence microscopic observation using reactive oxygen species (ROS)-specific fluorescence probe suggested that lycopene effectively reduced intracellular ROS level in LPS-stimulated RAW264.7 cells, but it was less-effective on ROS level in RAW264.7 cells stimulated with CEL-I. These results suggest that the pathways leading to increase in intracellular ROS level and subsequent NO and TNF-α secretion may be somewhat different between LPS- and CEL-I-treated RAW264.7 cells. This is the first report indicating that lycopene can inhibit the secretion of NO and TNF-α from RAW264.7 cells stimulated with CEL-I.