Abstract: Propolis is a resinous natural live product derived from plant exudates collected by honey bees. It has been extensively used in folk medicine. In the present study, the neuroprotective effects of propolis was investigated in the rat model of Parkinson’s disease. The PD rats which was induced by 6-OHDA were compared with control (C) and treatment groups with different dose of Propolis. After 4 weeks of follow-up, behavioral activity, tyrosine hydroxylase positive neurons in substantia nigra pars compacta, brain derived neurotrophic factor in serum and brain and stress oxidative factors such as superoxide dismutase, glutathione peroxidase activity, malondialdehyde and ferric reducing ability of plasma in the substantia nigra were analyzed. It was confirmed that 6-OHDA led to behavioral deficits, reduction in superoxide dismutase (6.02±0.1), glutathione peroxidase activity (0.12±0.01), ferric reducing ability of plasma (0.72±0.09) and the elevation of malondialdehyde levels (6.70±0.2) in the substantia nigra. When Propolis administered prior to 6-OHDA, improved motor coordination, increased superoxide dismutase (6.66±0.1), glutathione peroxidase (0.20±0.01) and ferric reducing ability of plasma (0.76±0.01) activity and reduced the content of malondialdehyde (6.2±0.1) compared with rat treated with 6-OHDA alone. Immunohistochemical studies showed that medication of propolis could prevent the loss of tyrosine hydroxylase positive neurons induced by 6-OHDA (107±5.77 vs 63±6.58). Decrease brain derived neurotrophic factor and some stress oxidative factors has an important effect in damage of tyrosine hydroxylase neurons in the brain. Propolis improves these factors and protects tyrosine hydroxylase neurons in the brain.