We examined whether interleukin‐1 (IL‐1), a multifunctional proinflammatory cytokine, progresses or regresses metastasis of lung cancer. Exogenous IL‐lβ enhanced expression of various cytokines (IL‐6, IL‐8, and vascular endothelial growth factor (VEGF)) and intracellular adhesion molecule‐1 (ICAM‐1) by A549, PC14, RERF‐LC‐AI, and SBC‐3 cells expressing IL‐1 receptors. A549 cells transduced with human IL‐1β‐gene with the growth‐hormone signaling‐peptide sequence (A549/IL‐1β) secreted a large amount of IL‐1β protein. Overexpression of IL‐1β resulted in augmentation of expression of the cytokines, ICAM‐1, and matrix metallo‐proteinase‐2 (MMP‐2). A549/IL‐1β cells intravenously inoculated into severe combined immunodeficiency (SCID) mice distributed to the lung more efficiently and developed lung metastasis much more rapidly than did control A549 cells. Treatment of SCID mice with anti‐IL‐1β antibody inhibited formation of lung metastasis by A549/IL‐1β cells. Moreover, A549/IL‐1β cells inoculated in the subcutis grew more rapidly, without necrosis, than did control A549 cells, which produced smaller tumors with central necrosis, suggesting involvement of angiogenesis in addition to enhanced binding in the high metastatic potential of A549/IL‐1β cells. Histological analyses showed that more host‐cell infiltration, fewer apoptotic cells, more vascularization, and higher MMP activity were observed in tumors derived from A549/IL‐1β cells, compared with tumors derived from control A549 cells. These findings suggest that IL‐1β facilitates metastasis of lung cancer via promoting multiple events, including adhesion, invasion and angiogenesis. (Cancer Sci 2003; 94: 244–252)