Aims: The total glucosides of paeony (TGP) are used to treat psoriasis in the clinic. However, its active components and mechanisms are not clear. Paeoniflorin is the main constituent of TGP. Thus, the anti-psoriasis effect of paeoniflorin was studied, and its mechanism was explored. Materials and methods: The effect of paeoniflorin was evaluated using a psoriasis-like model of guinea pigs. The levels of IL-6, IL-17A, IL-22, p38 MAPK, and ERK1/2 in HaCaT cells stimulated by lipopolysaccharide (LPS) were determined using RT-qPCR, enzyme linked immunosorbent assays (ELISA5) and western blot. Key finding: Compared with the control group, the model group showed edema, redness, and lesions in the ear upon stimulation with propranolol hydrochloride, and the Baker Score increased by 7-fold. Paeoniflorin ameliorated the lesion and decreased the Baker Score by 37% (p < 0.05). In vitro, paeoniflorin significantly inhibited the mRNA expression of IL-6, IL-17A and IL-22 at both 2.08 and 10.41 mu M (p < 0.01), and paeoniflorin had a marginal effect on the protein expression of IL-17A and IL-6. However, it inhibited the protein expression of IL-22 significantly, with inhibition ratios of 48.5% and 47.8% at 2.08 and 10.41 mu M, respectively (p < 0.05). This effect was achieved by inhibiting the phosphorylation of p38 MAPK. Significance: The results of this work demonstrated that paeoniflorin is the active components of TGP and support its use as a therapeutic compound for psoriasis therapy. (C) 2017 Elsevier Inc. All rights reserved.