Depression is a common mental disorder, however, no practical biological marker exists to date. In this study, we explored the possibility of peripheral 5-hydroxytryptamine (5-HT) and its receptors being biomarkers for depression diagnosis and treatment response. We assayed the 5-HT level and expression of 5-HT receptors mRNA in blood and in the nuclei of brain tissues of Sprague-Dawley rats, and analyzed the correlations between peripheral and central. Our results demonstrated that there was a significant reduction in platelet 5-HT level (but not in plasma 5-HT level) in depressive rats treated with citalopram, and there was also a higher 5-HT level in hippocampus of depressive rats. However, the level of 5-HT in blood had no significantly correlation with that in the nuclei of brain tissues. There was no significant difference of 5-HT1aR and 5-HT2aR mRNA expression in blood or in the nuclei of brain tissues. 5-HT1a receptor mRNA expression in blood is significantly correlated with that in striatum, and there were no significant correlation of 5-HT2a receptor expression between blood and brain tissue. Our study suggested that although platelet 5-HT level could not reflect the central serotonergic function directly, it might response to citalopram treatment, so it may be a candidate biomarker of treatment response to depression. Although the expression of 5-HT1aR mRNA in blood could reflect the expression in striatum, it is not an appropriate biomarker for depression.