In the current study, we investigated changes in key molecules from several signaling pathways in NSCLC cells cocultured with CAFs and found that the MAPK/ERK1/2 and PI3K/AKT signaling pathways were activated by leptin produced by CAFs, which demonstrated that the functions of paracrine leptin in NSCLC were similar to those in the same pattern with that of the serum leptin to in other cancers. This evidence concerns the gene MAPK3 and cancer.