Background: At present, L-DOPA remained the gold standard therapy for motor symptoms of Parkinson's disease (PD) patients. However, prolonged administration of L-DOPA led to the development of dyskinesia. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), has been widely used to relieve pain and inflammation. Recent studies indicated that aspirin produced neuroprotection against DA neuronal loss in PD animal model. Methods: Rats lesioned with 6-hydroxydopamine (6-OHDA) in substantia nigra were employed and treated with L-DOPA and aspirin for 21 days. The movement disorders elicited by L-DOPA were determined by the abnormal involuntary movements (AIM) scores analysis. Finding: In 6-OHDA lesioned rat PD model, aspirin or L-DOPA evoked DA neuroprotection 7 days after treatment. Co-administration of aspirin and L-DOPA still conferred neuroprotection. In addition, aspirin attenuated the development of LID, as evidenced by the decreased AIM scores without interfering with L-DOPA efficacy 21 days after treatment. Furthermore, aspirin combined with L-DOPA inhibited microglia and astroglia activation and the subsequent neuroinflammatory responses. Importantly, aspirin didn't produce side effects during this neuroprotection. Interpretation: These results suggest that aspirin might have beneficial potential to attenuate L-DOPA efficacy and alleviate LID in PD. Funding Statement: National Natural Science Foundation of China (No. 81760658), foundation for High-level Innovative Talents of Guizhou Province (No. 20164027), Shijingshan's Tutor Studio of Pharmacology (No. GZS-201607), Innovation Research Group project of Education Department of Guizhou Province (No. 2016038), foundation for Excellent Young Talents of Zunyi Medical University (No.201603). Declaration of Interests: The authors have declared no any conflict of interests. Ethics Approval Statement: All animal experiments were performed in accordance with Chinese Guidelines of Animal Care and Welfare, and the present study was approved by the Animal Care and Use Committee of Zunyi Medical University (Zunyi, China).