To analyze total glycosides of paeony’s (TGP) influence on expression of VEGF mRNA in skin tissue and peripheral blood of Psoriasis mice and to explore the possible mechanism of TGP's treatment of Psoriasis. 60 mice were divided into six groups: Model group, treatment group, blank group and lowdose, middle-dose and high-dose TGP group, the mice in every group were applied 5% imiquimod cream on their backs except those in blank group. All the mice in each group were executed on the 8th day except those in treatment group, which were offered with middle-dose TGP treatment, continuously applied 5% imiquimod cream and executed until the skin lesion has vanished entirely. VEGF expression levels among different groups were surveyed by quantitative real-time PCR. On the 15th day of experiment, the skin lesion of mice in treatment group fades, and the tissue pathology doesn’t show any abnormality. The VEGF mRNA expression amounts of mice skin tissue and peripheral blood from model group are all higher than those from blank group and the VEGF mRNA expression amounts of mice skin tissue from blank group, treatment group, high-dose, and middle-dose TGP group are all lower than those from model group, with a statistical significant (P<0.05). Therefore, TGP can produce a therapeutic effect on psoriatic lesions by inhibiting expression of VEGF mRNA in the psoriasis model.