<p>This study investigates the antitumor effects and immunomodulatory mechanisms of <i>Astragalus membranaceus</i> (AM) injection at Zusanli (ST36) acupoint in a mouse model of lung cancer with chronic obstructive pulmonary disease (LC-COPD). Mice were divided into LC-COPD and lung cancer-only groups, each further subdivided into model, AM, cisplatin (DDP), and AM + DDP subgroups. Tumor growth, lung metastasis, and survival were assessed. Expression of PD-1 and TIM-3 in tumor tissues was evaluated by immunohistochemistry and Western blot. The proportions of PD-1⁺ and PD-1⁺ TIM-3⁺ CD8⁺ and CD4⁺ T cells were analyzed by flow cytometry. AM injection at Zusanli alone inhibited tumor weight to a similar extent in both the LC-COPD and lung cancer-only groups, but conferred greater inhibition of pulmonary metastasis and prolonged survival only the LC-COPD group. Combining this therapy with DDP further reduced tumor weight and metastasis and extended survival, outperforming either single treatment in the LC-COPD group only. AM intervention downregulated PD-1 and TIM-3 expression in tumor tissues and reduced the proportions of PD-1⁺ and PD-1⁺ TIM-3⁺ CD8⁺ and CD4⁺ T cells. These immunomodulatory effects were greater in the LC-COPD group. In the LC-COPD model, AM injection at Zusanli significantly downregulated PD-1 and TIM-3 expression and alleviated T cell exhaustion. This may explain why LC-COPD derives greater benefit from this therapy. The combination of this therapy with DDP enhanced anti-tumor efficacy, suggesting its promise as an effective treatment strategy for LC-COPD.</p>