The increasing incidence rate of breast cancer in the last few decades is known to be linked to the upward trend of obesity prevalence worldwide. The consumption of high-fat diet in particular has been correlated with postmenopausal breast cancer risk. The underlying mechanisms, using suitable and reliable experimental mouse model, however, is lacking. The current review aims to discuss the evidence available from mouse models on the effects of dietary fats intake on postmenopausal breast cancer. We will further discuss the biochemical mechanisms involved in the occurrence of postmenopausal breast cancer. In addition, the methodological considerations and their limitations in obesity-related postmenopausal breast cancer, such as choice of mouse models and breast cancer cell lines as well as the study duration will be reviewed. The current review will provide a platform for further development of new xenograft models which may offer the opportunity to investigate the mechanisms of postmenopausal breast cancer in a greater detail.