Rhus verniciflua Stokes (RVS) has traditionally been used as a food supplement and a traditional herbal medicine for centuries in Korea. This study attempted to evaluate the effects of RVS on the expression of Brain derived neurotrophic factor (BDNF) and Glial cell line-derived neurotrophic factor (GDNF) in SH-SY5Y cells and the rat brain. The results indicated that RVS is a potent inducer of Neurotrophic factor (NTF) production both in vitro and in vivo. Treatment with 10 µg/ml and 10 mg/kg RVS for 4 h of SH-SY5Y cells and rats yielded significant increases in BDNF and GDNF protein levels. We also detected BDNF and GDNF immunoreactive neurons in the rat brain. Both BDNF and GDNF-immunohistochemical staining was markedly enhanced in the animals treated with RVS. These results suggest that RVS serves as an ideal adjuvant in regard to regulating NTF expression, and can contribute to neuroprotection in neurodegenerative diseases.