Leptin is an adipokine encoded by theOb (obese) gene and predominantly produced by adipocytes. Theroles of both leptin and leptin receptor (ObR) in numerous pathophysiological conditions including mammary tumor (MT) development have been reported. To examine protein expression levels of leptin and its receptors (ObR) including thelong form, ObRb, in MT tissue and mammary fat pad of a transgenic mammary cancer mouse model. Further, we investigated whether theeffects of leptin on MT development are systemic or local. MMTV-TGF-α transgenic female mice were fed ad libitum from week 10up to week 74. Protein expression levels of leptin, ObR, and ObRb were measured in themammary tissue samples of 74-week old MMTV-TGF-α mice with and without MT (MT-positive/MT-negative) by Western blot analysis. Serum leptin levels were measured by using themouse adipokine LINCOplex kit 96-well plate assay. Protein expression levels of ObRb were significantly lower in MT as compared to control tissue of mammary gland. In addition, protein expression levels of leptin were significantly higher in theMT tissue of MT-positive mice compared to control tissue of MT-negative mice. However, ObR protein expression levels in tissues of mice with and without MT were similar. Serum leptin levels at different ages were not significantly different between thetwo groups. Leptin and ObRb in themammary tissue may play a critical role in themammary cancer development, while contribution of short ObR isoform may be less important.