Parkinson's disease (PD) is a progressive neurological disorder which is emanated by dopaminergic death cell and depletion. Curcumin as a nontoxic matter has antioxidant, anti-inflammatory, and antiproliferative activities, and it involves antioxidant property same to vitamins C and E. In this study, we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (50 mg/kg) was injected intraperitoneally (i.p.) once daily for a period of 10 days beginning 5 days prior to Hcy (2 μmol/μl) intracerebroventricular (i.c.v.) injection in rats. The studies included immunohistological and locomotor activity tests. These results suggest that homocysteine intracerebroventricular administration (2 μmol/μl i.c.v.) may induce changes in rat brain, and subsequently, polyphenol treatment curcumin 50 mg/kg (i.p.) was capable in improving locomotor function in insulted animal by protecting the nervous system against homocysteine toxicity.