Objective To investigate the effects of vascular endothelial growth factor (VEGF) on disused bone loss. Methods Tail-suspended (TS) rat models were established and evenly divided into TS+Saline group, TS+VEGF group, CON+Saline group and CON+VEGF group. During the experiment, VEGF or equivalent amount of saline was injected into the gastrocnemius muscle of the rats’ right tibia twice a week for each rat. After four weeks, the proximal tibia of the rats was scanned by micro-CT. The bone mineral density (BMD) of the trabecular bone and cortical bone, micro-structure parameters of the trabecular bone, such as bone volume per trabecular volume (BV/TV), tabecular number (Tb.N), trabecular spacing (Tb.Sp), structure model index (SMI), and cortical thickness were used as evaluation indices to study the influence of VEGF on bone loss in the proximal tibia of tail-suspended rats. Results Compared with the control rats, in tail-suspended groups, the apparent BMD, BV/TV, Tb.N, SMI of trabecular bone and the cortical thickness all decreased significantly, while the Tb.Sp and SMI significantly increased, which showed that tail suspension would cause bone loss, while the injection of VEGF would alleviate the loss of trabecular bone in tail-suspended rats. Conclusions There might exist some relationship between the status of blood supply and bone remodeling process, and by improving the status of vascular system, the disused bone loss can be alleviated.