In Parkinson's disease (PD), post-mortem examination reveals a loss of dopaminergic (DA) neurons in the substantia nigra (SN) associated with a massive astrogliosis and the presence of activated microglial cells. Similarly, microglial activation has also been reported to be associated with the loss of DA neurons in animal models of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, annonacine and lipopolysaccharide (LPS). Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, raising the possibility that toxic substances released by glial cells could be involved in the propagation of neuronal degeneration. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in PD.