Cranberry juice (CJ) is a rich source of polyphenols with strong antioxidant activity believed to contribute to this fruit's wide range of health benefits. However, to date, our knowledge of cranberry neuroprotective potential is very scarce and limited to only a few in vitro studies. Recently, we have reported that treatment of rats with CJ controls oxidative stress in several organs with the most noticeable effect in the brain. In this study, we examined the capability of cranberry juice for protection against Parkinson's disease (PD) in a rat model of parkinsonism induced by rotenone (ROT). Wistar rats were given the combined treatment with ROT and cranberry juice (CJ) (200 and 500 mg/kg/day p.o) for 35 days. To evaluate its neuroprotective effect, microscopic examination, determination of inflammation and apoptosis markers, and α-synuclein level were performed in the midbrain. Our results indicated that CJ treatment provided neuroprotection as evidenced by the enhancement of neuronal survival, which correlated well with decreased expression of pro-apoptotic proteins including caspase 9, Bax, and cytochrome c as well as declined α-synuclein level. However, the expression of tumor necrosis factor-alpha was similar across all groups with no statistically significant differences.