Animal models of Parkinson’s disease are essential to explore pathophysiological hypotheses and to test new treatment options, including neurotrophic factors. Catecholaminergic neurotoxins used to generate such models are 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These neurotoxins predominantly kill dopaminergic neurons through oxidative damage and mitochondrial failure, although 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine fails to induce a significant dopaminergic neurodegeneration in rats. The present chapter describes a protocol for the 6-hydroxydopamine rat model based on stereotaxic injection performed only unilaterally, which mimics an early-to-mid stage of the disease.