The molecular aetiology of steroid-induced osteonecrosis (ON) is unclear. The aim of this study was to investigate changes in the femoral head blood supply and vascular endothelial growth factor (VEGF) protein levels following steroid-induced ON of rabbit femoral heads in the early stage of the disease, and to investigate a possible mechanism for ON. Using a classic protocol, ON was induced in 30 male 28-week old New Zealand white rabbits. An additional 15 untreated rabbits served as controls. Change of blood supply in the proximal femur was assessed by dynamic magnetic resonance imaging and microangiography. The VEGF protein and mRNA levels were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. After 6 weeks, the results indicated that VEGF protein and mRNA levels were significantly lower and femoral head blood supply had also decreased significantly in ON(+) rabbits compared with controls. The down-regulation of VEGF may play a critical role in the disease process of ON.