Liver regeneration is dependent upon coordinated proliferation of hepatocytes and endothelial cells. The hormone prolactin (PRL) is a potent liver mitogen and a stimulator of blood vessel growth (angiogenesis). Here, we examine whether increased levels of circulating PRL can promote liver regeneration after partial hepatectomy via stimulation of both, cell proliferation and expression of vascular endothelial growth factor (VEGF), a major determinant of liver angiogenesis. Male rats were implanted with two anterior pituitary glands (AP) under the kidney capsule to increase circulating PRL levels, and after fifteen days subjected to a 30 percent partial hepatectomy (PH) for one or three days. Liver regeneration was determined as liver weight, cell proliferation was assayed by western-blot and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), expression of VEGF was determined by RT-PCR, and ELISA was used to measure PRL levels. On postoperative day three, higher PRL levels in AP-implanted rats correlated with a significant increase in liver remnant weight with respect to both sham and 30 percent PH controls. The increase in liver weight in AP-implanted-30 percent PH rats was similar to that in 70 percent-PH rats. Higher PCNA levels and VEGF expression were found in AP-implanted rats at postoperative day one. In conclusion, PRL promotes liver regeneration, and this action may be secondary to the stimulatory effect of PRL on hepatocyte proliferation and VEGF-induced angiogenesis. These effects could have potential value for the control of liver diseases that require regeneration, such as fulminant hepatitis or after liver injury.