Abstract： Objective To explore the role ofpostsynaptic density 95 (PSD-95) in Parkinsonian rat models receiving chronic L-dopa treatment. Methods The hemi-parkinsonian rat models were established by stereotaxically injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of 60 rats. Thirty-two of them were successfully induced into models with PD and equally randomized into PD group, L-dopa plus physiological saline treatment group, L-dopa plus PSD-95antisense oligonucleotide treatment group and L-dopa plus TE treatment group (n=8). The rats in the PD group were treated intraperitoneally with 0.2% ascorbic acid physiological saline water. The rats in the for 22 d. On the following 3 days, the rats were performed intraperitoneal injection of physiological saline water, injection of PSD-95 antisense oligodeoxynucleotide and TE buffer in the striatum,respectively. Another 8 rats were chosen as normal control group, only given solvent. Rotational reaction time and the largest number of revolutions within 5 minutes of rotation were estimated on the 25th d of injection. After rats being sacrificed, Mrna and protein expressions of PSD-95 at the corpus striatum were observed by RT-PCR and Western blotting, repectively. Results After chronic treatment with L-dopa methylester, the rotational reaction time was prolonged and the the largest number of revolutions within 5 minutes of rotation of PD rats was decreased in the L-dopa plus PSD-95 antisense oligodeoxynucleotide group on the 25th d, as compared with those in the L-dopa plus physiological saline water group and L-dopa plus TE group (P＜0.05). In the lesioned striatum of PD rats, the abundance of PSD-95 Mrna and protein expressions were statistically and evidently reduced as compared with those in the control group (P＜0.05). After chronic treatment of PD rats with L-dopa, the abundance of PSD-95mRNA and protein expressions were statistically and evidently increased as compared with that in the PD group (P＜0.05). Pretreatment with PSD-95 antisense oligodeoxynucleotide statistically and obviously reduced the abundance of PSD-95 protein expression as compared with pretreatment with chronic L-dopa (P＜0.05). Conclusion PSD-95 may play a significant role in the pathogenesis of motor complications of rats with PD receiving chronic L-dopa treatment.