Objective To investigate the effect of long-term environmental enrichment （EE） on depressed mood in a mouse Parkinson’s disease （PD） model induced by neurotoxin 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）.Methods A total of 40 seven-month-old male C57BL/6N mice were randomly divided into EE+MPTP （n=10）， EE+normal saline （NS）（n=10）， standard environment （SE）+MPTP （n=10）， and SE+NS （n=10） groups. After three months of intervention with EE or SE， the mice in the MPTP groups were subjected to neurotoxin MPTP （intraperitoneal injection， 30 mg/kg） once daily for 7 consecutive days for modeling. The mice in the NS groups were given intraperitoneal injection of the same amount of 0.9%NaCl as the control study. Behavioral methods were used to evaluate the behavioral manifestations of mice， and immunohistochemical staining was performed to observe the positive areal density values of tyrosine hydroxylase （TH） and 5-hydroxytryptamine 1A （5-HT_1A） receptor.Results The behavioral results showed that the mice in the MPTP groups had a significantly lower forced swimming score （P<0.01） and a significantly long erimmobility time in the tail suspension test （P<0.01） than those in the NS groups. The mice in the EE+MPTP group had significantly milder depression symptoms mentioned above than those in the SE+MPTP group （P<0.05）. The results of immunohistochemical staining showed that the mice in the SE+MPTP group and EE+MPTP group had significantly lower positive expression levels of TH and 5-HT_1A receptor than those in the NS groups （P<0.01）， while the mice in the EE+MPTP group had significantly smaller decreases in positive expression levels of TH and 5-HT_1A receptor than those in the SE+MPTP group （P<0.05）.Conclusions The behavioral abnormalities of MPTP mice and the reduction in TH positive areal density value suggested that the PD model was successfully established. The mice in the EE+MTPT group had significantly milder 5-HT_1A receptor damage than those in the SE+MPTP group， suggesting that environmental enrichment may alleviate the depressed mood in the MPTP-induced PD model in mice. ［Citation:Journal of International Neurology and Neurosurgery, 2021, 48(3): 239-243］