Abstract: Objective To investigate the effects of bevacizumab combined with concurrent chemoradiotherapy and metformin on the clinical effectiveness, adenosine monophosphate activated protein kinase (AMPK), vascular endothelial growth factor (VEGF) and serum chemerin of patients with non-small cell lung cancer (NSCLC). Methods A total of 120 NSCLC patients who were admitted to Liaoyou Baoshihua Hospital from February 2016 to February 2019 were enrolled. According to the random number table method, they were divided into two groups (n=60): a research group and a control group. The control group was given bevacizumab combined with concurrent chemoradiotherapy, while the research group was treated with metformin on the basis of the control group. Their clinical effectiveness and the levels of serum AMPK, VEGF and chemerin before and after treatment were compared. Results The research group presented remarkable improvement in clinical effectiveness rate, disease control rate, and quality of life, compared with the control group (P<0.05). After treatment, the research group showed significant increases in AMPK and decreases in VEGF, chemerin, insulin-like growth factor 1 (IGF-1), and mammalian target of rapamycin (mTOR), compared with the control group (P＜0.05). The research group also produced obviously increased immune cells (CD3⁺, CD4⁺ and CD4⁺/CD8⁺) and decreased CD8⁺ after treatment, compared with the control group (P＜0.05). There were statistical differences in adverse reactions between the two groups (P>0.05). The overall survival (OS) and progression-free survival (DFS) were longer for the research group than those in the control group (P<0.05). Conclusions Bevacizumab combined with concurrent chemoradiotherapy and metformin can effectively reduce the levels of serum VEGF and chemerin, and improve AMPK protein expression in NSCLC patients.