Objective To evaluate the effect of ginsenoside pre-treatment on serotonin (5-hydroxytryptamine,5-HT),5-HT2A receptor (5-HT2A R),and 5-HT transporter (serotonin transporter,SERT) in serum,platelet lysate and brain tissue homogenates in SD rats with myocardial infarction (MI) or depression.Methods Eighty SD rats were randomized treated with ginsenoside or normal saline (NS).After 4 weeks,the rats were,then,randomized to four subgroups:the MI,the depression,the MI in combination with depression and sham subgroups.5-HT,5-HT2A R and SERT levels were detected in serum,platelet or brain.Results In the NS pre-treatment groups,serum 5-HT levels in sham rats (237.1 ± 32.0)pg/ml were higher than in MI (58.0 ± 11.6) pg/ml,depression (72.8 ± 2.3) pg/ml,and MI with depression rats (62.5 ± 10.2) pg/ml (all P =0.000).Pre-treatment of ginsenoside increased serum and platelet 5-HT in MI,depression and MI with depression rats compared with each corresponding NS treated subgroups (all P ＜ 0.005).However,treatment of ginsenoside lowered the 5-HT2A R expression in MI,depression,and MI with depression subgroups both in platelet and brain tissue homogenates compared with each corresponding NS treated subgroups (all P ＜ 0.05).As to SERT in platelet,treatment of ginsenoside increased its levels in depression rats (P =0.019),but lowered the levels in MI rats (P =0.001) compared with NS treated rats.There were no differences in brain 5-HT and SERT between ginsenoside and NS treated groups.Conclusions The 5-HT system responses differently to ginsenoside treatment under different cardiac and mental stress conditions.Ginsenoside plays an important role in regulation of 5-HT system.