Aims: We tested the hypothesis whether vascular endothelial growth factor (VEGF-A) gene transfer is an appropriate way to enhance recruitment and activity of osteoblasts in vivo. Methods: We tested plasmid/ liposome and adenoviral gene transfer vectors in vitro and selected adenoviruses for in vivo experiments. Adenovirus vectors containing VEGF-A or lacZ genes (1.4x10¹⁰ pfu) were injected locally into right distal femurs of New Zealand White rabbits. Saline was injected into all contralateral distal femurs. One and three weeks after the gene transfers femurs were collected for analyzes. Trabecular bone hard tissue histo-morphometry was performed to analyze the effect of gene transfer on bone turnover. Results: X-Gal staining showed that up to twenty percent of the bone marrow cells were transfected. When compared to unilateral lacZ transfected trabecular bone at one week time point, VEGF-A bone had 8% less bone volume, 90% higher osteoblast number, 100% higher osteoblast surface, 125% higher osteoid volume and 70% less resorption surface. Corresponding parameters were 70% higher bone volume, 7% higher osteo-blast number, 30% higher osteoblast surface, 22% higher osteoid volume and 49% less resorption surface at week three. Conclusions: Our results suggest that adenovirus-mediated VEGF-A gene transfer induces bone formation via increasing osteoblast activity and maybe useful for the treatment of osteoporosis and other diseases that required efþcient osteogenic therapy.