As shown in the present study, 1) the two isoforms of TPH have a different spatial distribution, with TPH1 expressed predominantly in the peripheral tissues and TPH2 primarily localized in the central serotonergic neurons; 2) Tissues 5-HT concentrations and TPH1/2 expression were decreased in brain tissues in the rat model of depression; 3) Stress inhibited TPH2 expression in the depressive rats possibly due to an increase in the methylation of the TPH2 gene promoter in brain tissues. Here, TPH2 is linked to depressive disorder.