Vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and angiopoietin-1 (Ang-1) are angiogenic factors implicated in the development of the corpus luteum (CL). Each factor is reported to be regulated or influenced by leptin in non-ovarian tissues. Leptin is a potent satiety hormone that also has angiogenic properties. Both leptin and its receptor, Ob-Rb, have been identified in luteal tissue specifically during CL development. Therefore, it is hypothesized that leptin regulates angiogenesis through VEGF, Ang-1, and FGF-2 in the CL during different stages of the luteal phase. Cycling, crossbred caprine females were allocated to early (day 3; n=12), mid (day 10; n=8), and late (day 15; n=11) stages of the luteal phase for CL collection. Luteal tissue was frozen, parrafinized, or cultured with leptin (0, 10^-12, 10^-11, 10^-10, 10^-9, 10^-8 M) and analyzed for VEGF, Ang-1, FGF-2, and Ob-Rb mRNA using RT-PCR. Tissue was analyzed for VEGF, Ang-1, FGF-2, Ob-Rb, and leptin mRNA and protein at the time of tissue collection using RT-PCR and western blotting. VEGF and Ang-1 mRNA did not differ between days of the luteal phase; however, Ang-1 protein tended to decrease (P =0.08) from mid to late stages. FGF-2 mRNA increased (P=0.01) from early to mid and remained elevated at the late stage. Ob-Rb mRNA decreased (P=0.02) from early to mid; however, Ob-Rb increased ( P=0.0001) in late luteal tissue. Ob-Rb protein did not differ between days of the luteal phase. Leptin mRNA and protein were highest (P ≤0.01) during the early stage compared to mid and late stages. VEGF was localized to small luteal cells in early tissue, large luteal cells in late tissue, and vessels in mid and late tissue. Ob-Rb and Ang-1 were predominantly localized to luteal cells, large and small, throughout the luteal phase, Ob-Rb was localized to vessels in early and late tissue, and Ang-1 was found in vessels throughout the luteal phase. FGF-2 was localized to small luteal cells throughout the luteal phase and vessels in early tissue. In early stage cell cultures, leptin increased (P≤0.05) FGF-2 and tended to increase (P=0.09) VEGF mRNA. In day 10 cultures, leptin dose dependently increased (P≤0.04) VEGF; however in day 15 cultures, leptin decreased (P≤0.04) FGF-2 in late cultures. Leptin did not influence Ang-1 mRNA in vitro. Collectively, evidence suggests that leptin may be involved in the luteal angiogenic process through regulation of potent angiogenic hormones.