Infertility in females is the inability to become and maintain pregnancy, which can be caused by the abnormal development of a corpus luteum (CL). Abnormal development is linked to incomplete angiogenesis, which leads to an overall decrease in progesterone production. Angiogenesis is regulated by factors, such as fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and angiopoietin-1 (Ang-1) all of which are expressed in developing luteal tissue. Leptin, a potent satiety hormone, influences the expression of FGF and VEGF in non-ovarian tissue, and is also produced in the CL. Hence, it is hypothesized that leptin influences the production of FGF-2, VEGF, and Ang-1 in the developing CL. The objectives of the study were to (1) characterize angiogenic factor expression in the developing porcine CL and (2) determine the effect of leptin on FGF-2, VEGF, and Ang-1 expression in dispersed luteal tissue. Thirty mature crossbred gilts of similar age were allocated to one of five treatments (days of CL development: d 3, 4, 5, 6, or 7 of the estrous cycle; n=6/day) for tissue collection. Gilts were checked twice daily for classical, behavioral estrus using a boar for detection. Blood samples were collected on the day of CL harvest for serum progesterone analysis. Luteal tissue was divided and either embedded for immunohistochemistry, frozen in liquid nitrogen, or enzymatically digested and dispersed for culture. Dispersed cells were cultured with or without leptin (0, 10^-12, 10 ^-11, 10^-10, 10^-9, 10^-8 M; n = 3 wells/dose/gilt) for 24 hrs. Total expression for VEGF, FGF-2, Ang-1, and the leptin receptor (OB-Rb) was determined in all samples. All angiogenic factors and OB-Rb were localized to vascular endothelial cells, small luteal cells and large luteal cells; however, concentration and predominant cellular location varied by day of development. The expression of FGF-2 was highest (P = 0.05) on day 6 and leptin increased linearly (P = 0.005) as the CL developed. Leptin dose dependently decreased (P ≤ 0.05) VEGF, FGF-2 and Ang-1, relative to day of luteal development, by 10, 17 and 16.8%, respectively. Therefore, leptin appears to be involved in the angiogenic process in developing CL tissue.