Angiopoietin-1 (Ang-1) is an important angiogenic factor that has not been thoroughly studied in the primate endometrium. We evaluated the endometrial expression of Ang-1 and its receptor, Tie2, during induced menstrual cycles in rhesus macaques. Tie2 expression was confined to the vascular endothelium without marked change during the cycle. However, Ang-1 expression varied considerably during the cycle. In the proliferative phase, Ang-1 was only expressed in the basal zone glands, and this expression was estradiol (E2) dependent. In the early- to mid-secretory phase, Ang-1 expression spread to the upper glands, luminal epithelium and the vascular smooth muscle cells (VSMC) of spiral arteries. In the late secretory phase, the signal disappeared from the glands but remained elevated in the VSMC of spiral arteries. Notably, there was a significant correlation between VSMC proliferation and Ang-1 expression in the VSMC of the spiral arteries. Progesterone (P) withdrawal in the early secretory phase induced a decline in Ang-1 expression in the glands and VSMC of spiral arteries along with a complete suppression of VSMC proliferation. These data suggest, for the first time, that Ang-1 may play a key role in the P-dependent growth of the unique spiral arteries in the primate endometrium.