Objective <p>This paper aimed to unravel the effect of metformin on vascular endothelial injury in patients with non-small cell lung cancer (NSCLC) treated with chemotherapy combined with bevacizumab.</p> Methods <p>We recruited 120 NSCLC patients and then classified into A and B groups (<i>n</i> = 60 cases). A group was treated with chemotherapy + bevacizumab + metformin, and B group was treated with chemotherapy + bevacizumab. The efficacy, pro-inflammatory factors, immune factors, and markers of vascular endothelial injury before and after treatment were compared between the two groups. The incidence of adverse reactions and prognostic 1-year survival status during the treatment period in both groups were counted.</p> Results <p>Higher ORR and DCR were observed in Group A relative to Group B. TNF-α, IL-2, IL-12, ET-1, TM, and vWF were elevated in both groups after treatment, but were lower in Group A than in Group B. CD³⁺, CD4⁺, and CD⁴⁺/CD⁸⁺ were reduced in both groups after treatment, but were higher in Group A than in Group B. OS and DFS were higher in Group A than in Group B.</p> Conclusion <p>Metformin has some anti-inflammatory and immunoprotective effects on NSCLC patients treated with chemotherapy combined with bevacizumab, which may help to attenuate the vascular endothelial injury induced by chemotherapy and bevacizumab treatment and further improve the prognosis.</p>