BACKGROUND: Parkinson's disease (PD) is one of the prevalent debilitating neurodegenerative disor- ders. Accordingly, researchers are working on methods to modify PD progression. Previously, the neuro- protective effects of betaine, as a methyl donor agent in homocysteine metabolism, have been demonstrated in animal models of chronic cerebral hypoperfusion and memory deficits. OBJECTIVES: It was aimed to investigate the neuroprotective effects of betaine in an animal model of PD. METHODS: In male Wistar rats under two-week course of oral betaine administration (50, 100, and 200 mg/kg per day), the behavioral, biochemical, and histological evaluations were conducted one week follow- ing unilateral nigral 6-OHDA injection. RESUTLS: Betaine administration with dose of 200 mg/kg, one week before and after 6-OHDA lesioning, was associated with a meaningful reduction in the plasma levels of homocysteine (Hcy) in comparison with the control and sham groups (P < 0.05). Our evaluations revealed a remarkable improvement in motor asymmetry induced by apomorphine in the rats under treatment of betaine 200 mg/kg. Moreover, in this group, a significant decrease of malondyaldehyde (MDA) concentrations was detected in the brain tissues, as well as a significantly diminished neuronal cell loss (percent) in substantia nigra pars compacta (P < 0.05). The results of 50 and 100 mg/kg betaine groups were not significant. CONCLUSIONS: Altogether, our findings indicate the antioxidant neuroprotective effects of betaine in this animal model of PD and it is in concordance with betaine properties in decreasing the plasma levels and possible neurotoxic effects of Hcy.