Background: Bushen Tianjing Recipe (BTR) is a traditional Chinese herbal medicine that has been prescribed for premature ovarian failure (POF) for decades in China. Nevertheless, little is known regarding its underlying molecular mechanism. In the present study, we investigated the effects of BTR in a tripterygium glycoside (TG)-induced-POF rat model. Methods: Three doses of BTR were administered via intragastric gavage to adult female Sprague-Dawley (SD) rats with TG-induced POF. After 15 days of treatment, the estrous cycle was examined by vaginal smear analysis. Serum levels of estradiol, follicle-stimulating hormone, progesterone, and testosterone were measured by radioimmunoassay. Histological analysis and assessment of apoptosis were performed after hematoxylin and eosin staining of ovarian tissue sections. The expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), anti-apoptotic factor Bcl-2, and pro-apoptotic factors Bax and caspase 3 in ovaries of animals was examined by an immunohistochemistry process. Results: BTR not only reverted an abnormal estrous cycle and decreased the ovary index in POF rats but also improved the abnormal secretion of reproductive hormones associated with POF. In addition, treatment with BTR can protect ovaries from TG-induced damage, induce intraovarian expression of VEGF and VEGFR2, and regulate intraovarian expression of apoptosis-related proteins. Conclusions: Our results show that BTR is effective in the treatment of TG-induced POF rats. Promotion of angiogenesis and anti-apoptosis are most likely to contribute to the effects of BTR against POF.