Objective There is increasing interest in interactions between the nigrostriatal dopamine (NSD) system and the circadian system in Parkinsons disease.The two systems are mainly involved in neurotransmitters such as dopamine (DA) and melatonin (MLT).The purpose of our study was to investigate interactions between DA and MLT in the lesioned and intact NSD pathway of unilateral 6-hydroxydopamine (6-OHDA)-lesioned model rats.Methods Extracellular levels of DA and its metabolites DOPAC and HVA, as well as MLT in the lesioned-side striatum of unilateral 6-OHDA-lesioned rats were dynamically measured by mierodialysis with HPLC.Homogenate contents of these neurotransmitters in lesioned and intact sides of midbrain and striatum, as well as pineal gland of model rats were assayed by HPLC at different times post-lesion, Results (1) Extracellular DA, DOPAC and HVA levels in the lesioned-side striatum of 6-OHDA-lesioned rats declined evidently, while MLT levels in the lesioned side increased distinctly at 10:00 and 22:00 compared with the controls.(2) Homogenate contents of DA, DOPAC and HVA in the lesioned-side midbrain and striatum of model rats decreased sharply, while DA, DOPAC and HVA contents in the intact side had no significant changes compared with the controls.Homogenate contents of MLT at 10:00 and 22:00 in both sides of midbrain and striatum, as well as pineal gland of model rats increased obviously contrast to the controls, and MLT contents in the lesioned side increased distinctly contrast to the intact side.Conclusion These data suggest that MLT might play different roles in the lesioned and intact NSD pathway of unilateral 6-OHDA-lesioned rats.High levels of MLT may not protect dopaminergic neurons from oxidative stress in the lesioned NSD pathway of 6-OHDA-lesioned rats and may even decrease the release of DA, while relative high levels of MLT may still exert antioxidant effect on the intact NSD pathway.