BACKGROUND Local application of bisphosphonates has been proven to be safer than systemic administration to promote implant fixation. The objective of this study was to introduce such a simple, convenient and efficient method to enhance titanium (Ti) implant osseointegration in ovariectomized (OVX) rats. METHODS Twenty female Sprague-Dawley rats sequentially underwent bilateral ovariectomy and tibia implantation, and injection of 30 µg/implant zoledronic acid (ZOL) at the site of implantation was performed. At the end of the study, the tibiae, mandibles, femurs and vertebrae were harvested for dual energy X-ray absorptiometry, histology and micro-computed tomography examination. RESULTS Ovariectomized rats showed poor bone density, bone mass and trabecular microstructure. OVX + ZOL rats were characterized by significantly improved peri-implant bone area (1.72-fold), bone contact (2.30-fold), bone mineral density (1.57-fold) and bone mineral content (1.67-fold), as well as moderately increased bone volume to total volume ratio (1.34-fold), percentage osteointegration (1.54-fold), connectivity density (1.45-fold), and trabecular number (1.43-fold), but decreased trabecular separation (57.69%) when compared with the control levels (p < 0.05). No histological signs of jaw osteonecrosis were observed in the rats treated with ZOL, and there was no significant difference between the OVX group and OVX + ZOL group in the bone mass of the mandible, femur and 5th lumbar vertebra (p > 0.05). In addition, the overproduction of osteoporosis-induced advanced glycation end-products (AGEs) was completely prevented by local treatment with 30 µg/implant ZOL. CONCLUSIONS A local, one time, low-dose injection of ZOL at the site of implantation is able to promote the osseointegration of Ti implants following postmenopausal osteoporosis, and this action may be partly mediated by inhibition of the osteoporosis-induced AGE overproduction in the bone marrow.