Chronic l-3,4-dihydroxyphenylalanine (l-DOPA) treatment of Parkinson's disease (PD) often leads to debilitating involuntary movements, termed l-DOPA-induced dyskinesia (LID), about which the rodent analog, the abnormal involuntary movements (AIMs), has been associated consistently with an activation of the Ras-extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase signaling pathway. Previous studies have shown that lovastatin, a specific inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, can also inhibit Ras isoprenylation and activity and subsequently the phosphorylation of ERK1/2 (pERK1/2). We hypothesized that lovastatin treatment-commenced previous l-DOPA exposure could reduce AIM incidence and severity in the 6-hydroxydopamine (6-OHDA) rat model of PD by secondarily preventing the l-DOPA/Benserazide-induced increase in pERK1 levels. The lovastatin-l-DOPA/Benserazide-treated 6-OHDA animals displayed less severe rotational behavior as well as a dramatic reduction in AIM severity than the l-DOPA/Benserazide-treated ones. Such lower AIM severity was associated with a decrease in l-DOPA-induced increase in the following: (1) striatal pERK1 and (2) ΔFosB levels, and (3) theta/α oscillations of substantia nigra pas reticulata (SNr) neurons as well as (4) a normalization of SNr firing frequency. Those results strongly suggest that lovastatin might represent a treatment option for managing LID in PD.