Tetrabromobisphenol A (TBBPA), an emerging organic pollutant widely detected in human samples, has a positive correlation with the development of endometrial cancer (EC), but its underlying mechanisms have not yet been fully elucidated. Tumor-associated macrophages (TAM), one of the most vital components in tumor microenvironment (TME), play regulatory roles in the progression of EC. Consequently, this study mainly focuses on the macrophage polarization in TME to unveil the influence of TBBPA on the progression of EC and involved mechanisms. Primarily, low doses of TBBPA treatment up-regulated M2-like phenotype biomarkers in macrophage. The data from in vitro co-culture models suggested TBBPA-driven M2 macrophage polarization was responsible for the EC deterioration. Results from in vivo study further confirmed the malignant proliferation of EC promoted by TBBPA. Mechanistically, TBBPA-mediated miR-19a bound to the 3′-UTR regions of SOCS1, resulting in down-regulation of SOCS1 followed by the phosphorylation of JAK and STAT6. The present study not only revealed for the first time the molecular mechanism of TBBPA-induced EC’s deterioration based on macrophage polarization, but also established co-culture models, thus providing a further evaluation method for the exploration of environmental pollutants-induced tumor effects from the role of TME.