BACKGROUND: Recent studies described inflammation play a role in the abnormal involuntary movements that occur as a consequence of the chronic therapy for Parkinson’s disease through the dopamine precursor 3,4-dihydroxyphenyl-L-alanine (L-DOPA). Exogenously administered corticosterone, which inhibit cyclooxygenase (COX) activity, decrease L-DOPA-induced dyskinesia in unilateral dopamine-depleted rats. Between many inflammatory factors found in the Parkinson’s disease brain, the inducible isoform COX-2 is a critical enzyme in the mechanism of central nervous system inflammation. In this study we examined the effects of chronic L-DOPA treatment on the appearance of the COX-2 in the striatum of C57BL/6Jmice brain. METHODS: Dyskinetic symptoms were triggered by repetitive administration of a constant dose of L-DOPA (25 mg/kg, twice a day, for 25 days) in unilaterally 6-hydroxydopamine (6-OHDA) lesioned (striatum) adult male mice (25-30gr, n=6-8/group). Lesioned or sham animals were treated chronically (25 days) with either saline or L-DOPA (25mg/kg, i.p. +benseraside). The animals were anaesthetised with a mixture of ketamine (100mg kg-1) and xilazine (14mg kg-1, both i.m.). After perfusion and fixation, the brains were cut, immuno- stained for tyrosine hydroxylase (TH) immunoreactivity (ir) Cyclooxigenase-2 (COX-2)-ir in the striatum and substantia nigra. Comparisons were made between controls (saline microinjected) lesioned (6-OHDA microinjected) and dyskinetic (6-OHDA lesioned, L-DOPA-treated) and non-dyskinetic (6-OHDA lesioned, saline-treated) mice . RESULTS: Dyskinetic symptoms appear toward the end of the first week of treatment. TH-ir and COX-2-ir were found in neurons in the striatum after dopamine depletion. Dyskinesia was associated with L-DOPA-induced changes in the TH-ir and COX-2-ir in the neurons. Elevated COX-2 expression occurs within completely lesioned regions of the striatum, displaying an inverse correlation with remaining dopaminergic terminals. CONCLUSIONS: Our results suggest that the presence of COX-2-ir neurons in the striatum may underlie the long-duration response to L-DOPA in Parkinsonian mice. Promotion of these striatal COX-2-ir neurons might be involved in the development of aberrant striatal circuits and the appearance of L-DOPA induced dyskinesia