Abstract: Objective To explore the effect and significance of leptin on the expression of p-ERK1/2 and VEGF in A549 cells. Methods A549 cell line was treated with different concentration of letpin for 24，48 or 72 hours，respectively，and then cellular proliferation was evaluated by MTT method.VEGF expression in tumor cells was detected by immuno-histochemical method，Western blot analysis was used to detect both p-ERK1/2 and VEGF expressions. Results MTT assay showed that Leptin stimulated the proliferation of A549 cells in a does and time-dependent manner in vitro (P<0.05).The expression of VEGF was upregulated significantly in A549 cells treated by 80ng/ml or 160ng/ml Leptin (P<0.05)．Western blot showed that the protein expression of VEGF was significantly increased in a Leptin dose-dependent way．There was a positive correlation between p-ERK1/2 and VEGF (r=0.694，P<0.05). Conclusion Leptin stimulated proliferation of A549 cells and up-regulated VEGF protein expression partly through ERK1/2 pathway.