Cannulation of the thoracic lymph duct in experimental animals allows direct measurement of the lymphatic exposure of lymph-targeted drugs. When coupled with recent advances in genetically modified and diseased mouse models, this presents further opportunities to define changes in biological processes and disease in response to drug treatment. Although cannulation of the thoracic lymph duct in mice is inherently challenging because of the small size and delicate nature of the duct, it can be further confounded by anatomical variations between animals. In this communication, we present our observations on the anatomical features of the thoracic lymph duct between mice of different strains and genders, and discuss the impact of these features on the "cannulatability" of the duct. We also provide some technical tips to help guide other investigators to deliver higher experimental success rates.