Breast adipose tissue is an active component that supports mammary architecture, development, and local hormonal homeostasis. In obesity, chronic adipose inflammation induces aromatase expression in the breast tumor microenvironment, thereby increasing local estrogen biosynthesis and potentially promoting cancer progression. Using a DMBA/MPA-induced mammary carcinogenesis model, we found that a high-fat diet (HFD) increased the levels of pro-inflammatory mediators in mammary tumor tissue and surrounding adipose tissue, accompanied by enhanced aromatase expression and local estrogen production. Transcriptome profiling of HFD tumors identified chemokine (C-X-C motif) ligand 2 (CXCL2) as the most strongly upregulated secreted factor. Treatment with recombinant CXCL2 resulted in increased aromatase expression in preadipocytes. Analysis of the public single-cell RNA-sequencing dataset revealed that macrophages are the predominant cell population expressing CXCL2 within the breast tumor microenvironment. To determine the functional relevance of CXCL2 in vivo, C57BL/6 mice were fed HFD and inoculated orthotopically with E0771 mammary carcinoma cells. Treatment with a CXCL2-neutralizing antibody significantly reduced tumor volume compared with its untreated obese controls. Collectively, our findings reveal a potential role for CXCL2 in inflammation-driven aromatase expression and breast cancer progression, highlighting the CXCL2 axis as a potential therapeutic target.