Objectives: Neutrophils, the most abundant leukocyte in the human body, plays an important role in the innate immune system working as the first responders to pathogens. Recent studies advanced the knowledge on the role of neutrophils in the tumor microenvironment (TME). In the TME, neutrophils play a dual role as anti-tumoral N1 or pro-tumoral N2 neutrophils. Here, I will discuss the multifaceted roles of neutrophils in the TME. Also, the effect of an herbal decoction composed of Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii, namely SH003 will be introduced as well. Methods: Six-week-old, male C57BL/6 mice were subcutaneously injected with LLC1 murine lung carcinoma cells. After 2 weeks, mice were randomly distributed into 4 groups (n=5-7 per group). SH003 (400 mg/kg/day) was administrated via oral gavage for additional 2 weeks. Then, the mice were sacrificed, blood and tumor tissues were harvested. Markers for apoptosis were studied by western blot. N1-N2 neutrophils and T cells in the TME were determined by flow cytometry. Neutrophil extracellular trap (NET) formation was studied by flow cytometry, serum analysis and western blot. Results: SH003 and cisplatin treatment both reduced the size of tumor tissue. When co-treated together, the anti tumor effect was enhanced. SH003 suppressed N2 neutrophils and increased N1 neutrophils in the TME, which effects showed synergism when combined with cisplatin. Cisplatin alone did not show significant suppression in NET formation, however SH003 and the co-treatment suppressed NET formation in the TME and the circulation system. Additionally, SH003 increased the cytotoxic T cell number. 54 Conclusion: SH003 is previously reported to exert anti-tumor effects by regulating cell death pathways in cancer. This study first reports its effect on neutrophil-focused TME regulation. Importantly, while cisplatin showed a powerful anti tumor effect but cannot suppress NET formation induced by LLC1 inoculation, SH003 showed synergistic effect with cisplatin on suppressing tumor growth by inhibiting excessive NET formation in the TME.