Epidemiological studies indicate that obesity is associated with poor outcomes in breast cancer. In our previous work, we demonstrated that a chronic consumption of a high fat diet increases solid tumor growth and metastasis in a spontaneous mammary cancer mouse model. In addition to higher tumor burdens and rates of metastases, mice fed a high fat diet showed elevated levels of adipocyte derived monocyte chemoattractant protein-1 (MCP-1) in the blood. We hypothesized that diet-induced obesity promotes mammary carcinogenesis by inducing an inflammatory and tumor-supportive microenvironment. We further compared chow fed lean MMTV(PyMT) mice with those fed 45.0% (w/w) high fat (HF) to investigate the impact of body adiposity and dietary nutrient overload on levels of MCP-1 in tissue, tumor associated macrophages (TAMs) and for the degree of microvessel density. We analyzed early and late carcinoma stage tumors together with adipose tissue from mice fed HF and control diets in order to identify possible sources of MCP-1 production. MCP-1 levels in tumors of mice differed significantly by cancer stage and diet, with late stage tumors showing more MCP-1 (P<0.05). Moreover, MCP-1 production was elevated in adipose tissue of obese mice compared to lean mice. Tumors and adjacent adipose were stained with CD68 and the numbers of TAMs were quantified. Significantly more TAMs (P<0.05) were found within tumor beds and more crown-like structures were evident in adipose tissue from obese mice at both early and late stage carcinoma. Tumor beds also showed increased microvessel density when stained with CD31. In summary, diet-induced obesity increased levels of MCP-1 in tumors and adipose with more macrophage infiltration and greater vascular density evident in mammary tumor beds. Taken together, these findings suggest that high body adiposity caused by diet-induced changes promote an inflammatory and tumor-supportive microenvironment in breast cancer. NIH P20 RR016440, P30 R032138/GM103488, and P20 RR016477 Citation Format: Emily Ngan, Alessandra Pacilli, Eva Marshall, Kirstie Cutlip, James Coad, Amanda Ammer, Linda Vona-Davis. Diet-induced obesity increases tumor levels of MCP-1, macrophage infiltration and microvessel density in a murine model of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1549. doi:10.1158/1538-7445.AM2013-1549