Study design. The protective effects of the natural antiox-idant caffeic acid (CA) on behavioral tasks and lipid peroxidation were tested in an excitotoxic model produced by unilateral intrastriatal injection of quinolinic acid (QUIN), and in striatal slices incubated in the presence of the same toxin. CA (20 mg/kg) was administered intraperitoneally to rats every day for five days; then, rats received QUIN (240 nmol/µL). Six days later, motor asymmetry was quantified by the preferential use of forelimbs and the circling behavior tests. Rat striatal slices (300 µm thick) were incubated in the presence of CA (30–300 µM) and/or QUIN (100 µM) to estimate oxidative stress. Results. QUIN induced motor asymmetry in lesioned rats and increased lipid peroxidation in striatal slices when compared to control values. CA prevented the QUIN-induced toxic endpoints in a concentration-dependent manner. Conclusion. Our results support the neuroprotective role of CA in neurotoxic paradigms recruiting excitotoxic events.