A growing body of evidence suggests that chronic inflammation contributes to cancer development and progression. Tumor-derived immunoinflammatory cytokines help tumor cells escape immune control and limit the success of immunotherapy. Leptin has been proven to promote cancer progression by inducing cancer cell proliferation and invasion. However, the proinflammatory effects of leptin on lung cancer cells have not yet been fully elucidated. In this study, we demonstrated that human lung cancer A549 and H157 cells express leptin receptors Ob-Ra and Ob-Rb, and that leptin stimulation increases the production of immunoinflammatory cytokines: vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and prostaglandin (PGE2). Moreover, leptin stimulation activated the JAK/STAT3, PI3K/AKT and MEK1/2 signaling pathways, which contributed to VEGF, IL-6 and PGE2 production. Besides increasing immunoinflammatory cytokines, leptin also protected human lung cancer cells from tumor necrosis factor-related apoptosis-induced ligand-mediated cytotoxic death. Thus, we conclude that leptin promotes the immune escape of lung cancer by inducing proinflammatory cytokines and resistance to apoptosis.