Background: Transcranial direct current stimulation (tDCS) has been proven to be able to modulate motor cortical plasticity might have potential as an alternative, adjunctive therapy for Parkinson's disease (PD). However, the efficacy of tDCS in PD is still uncertain. A disease animal model may be useful to clarify the existence of a treatment effect and to explore an effective therapeutic strategy using tDCS protocols. Objective: The current study was designed to identify the comprehensive therapeutic effects of tDCS in 6-hydroxydopamine (6-OHDA)-lesioned PD rats. Methods: Following early and long-term tDCS application (starting 24 h after PD lesion, 300 μA anodal tDCS, 20 min/day, 5 days/week) in awake PD animals for a total of 4 weeks, the effects of tDCS on motor and non-motor behaviors as well as dopaminergic neuron degeneration levels, were identified. Results: We found that the 4-week tDCS intervention significantly alleviated 6-OHDA-induced motor deficits in locomotor activity, akinesia, gait pattern and anxiety-like behavior, but not in apomorphine-induced rotations, recognition memory and depression-like behavior. Immunohistochemically, tyrosine hydroxylase (TH)-positive neurons in the substantia nigra were significantly preserved in the tDCS intervention group. Conclusions: These results suggest that early and long-term tDCS could exert neuroprotective effects and reduce the aggravation of motor dysfunctions in a 6-OHDA-induced PD rat model. Furthermore, this preclinical model may enhance the promising possibility of the potential use of tDCS and serve as a translational platform to further identify the therapeutic mechanism of tDCS for PD or other neurological disorders.