Human insulin-like growth factor 1, a known regulator of bone formation, was investigated for its possible effect on membranous bone formation in a rat model. Full-thickness bone defects (10 x 10 x 1 mm) were created in the rat calvarium, and insulin-like growth factor 1 was administered by an osmotic minipump directly into the defect enclosed by the periosteum and dura mater. The dose of insulin-like growth factor 1 was 100 micrograms every 2 weeks. The defects were studied radiographically, macroscopically, and microscopically at 3, 6, 9, and 12 weeks. The group treated with insulin-like growth factor 1 showed qualitative and quantitative differences when compared with the control group. The amount of new bone formation in the group treated with insulin-like growth factor 1 was significantly larger than that of the control group. In the insulin-like growth factor 1 group, the location of new bone formation occurred in the center and at the margin of the bone defect. In the control group, bone was formed only around the margin of the bone defect. This study suggests that insulin-like growth factor 1 improved membranous bone healing in vivo and that insulin-like growth factor 1 makes mesenchymal precursor cells of bone differentiate directly into bone-forming cells.