Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects on dopaminergic (DA) neurons. In this study, we investigated whether the effects of VEGF were dose-dependent or not. First, VEGF was shown to be neuroprotective on 6-hydroxydopamine (6-OHDA)-treated murine DA neurons in vitro, although the 1 ng/ml of VEGF displayed more neuroprotective effects than 100 ng/ml. Furthermore, using 2 sizes of capsules (small/large) with different secreting quantities, 6-OHDA-treated rats receiving the small capsule filled with VEGF-secreting cells (BHK-VEGF) into the striatum showed a significant decrease in amphetamine-induced rotational behavior in number and a significant preservation of TH-positive fibers compared to those receiving the large BHK-VEGF capsule as well as those receiving BHK-Control capsule. Rats receiving the large BHK-VEGF capsule showed much more glial proliferation, angiogenesis, and brain edema around the capsule than those with the small one. High-dose administration of VEGF might cause poor circulation related to brain edema, although low-dose administration of VEGF displays neuroprotective effects on DA neurons. Our results demonstrate the importance of administration dose of VEGF, suggesting that low-dose administration of VEGF might be desirable for Parkinson's disease.