Astilbin has anti-inflammatory and immunoregulatory effects, and is frequently used in prescriptions treating psoriasis; however, the mechanism remains to be fully elucidated. In the present study, the effect of an astilbin microemulsion on a psoriasis-like model in guinea pigs was examined, and the underlying mechanism was investigated. The levels of interkeukin (IL)-6, IL-17A and IL-22 were determined using fluorescent reverse transcription-quantitative polymerase chain reaction analysis and enzyme-linked immunosorbent assays. The phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 was detected using western blot analysis. Compared with the untreated control, astilbin significantly ameliorated the lesions induced by propranolol hydrochloride. The effect of astilbin on cytokine levels were cytokine- and drug-concentration-dependent. At a concentration of 2.22 mu M, astilbin decreased the mRNA expression levels of IL-6, IL-17A and IL-22 in lipopolysaccharide (LPS)-induced HaCaT cells by 89, 69.1 and 69.3%, respectively. However, 2.22 mu M astilbin had no effect on the protein expression of IL-17A, and decreased the protein expression levels of IL-6 and IL-22 by 79.2 and 49.5%, respectively (P<0.05). At a concentration of 11.10 mu M, astilbin decreased the mRNA expression of IL-6, which was significantly induced by LPS, and significantly (P<0.05) decreased the protein expression levels of IL-6 and IL-22. Additionally, astilbin inhibited the LPS-induced activation of phosphorylated p38. These results suggested that astilbin has the potential to be developed into a topical drug for the treatment of psoriasis via the inhibition of inflammatory cytokines.