Psoriasis is an immune-mediated inflammatory skin disease that mainly affects the skin barrier. Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, long-term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti-inflammatory, anti-oxidant and anti-cancerous properties. However, it is unknown whether kaempferol is also anti-psoriatic. Here we established an imiquimod (IMQ)-induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesions and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis-like skin lesions induced by topical administration of IMQ. Kaempferol reduced CD3(+) T cell infiltration and gene expression of major proinflammatory cytokines, including interleukin (IL)-6, IL-17A and tumor necrosis factor (TNF)-alpha, in the psoriatic skin lesion. It also down-regulated proinflammatory nuclear factor kappa B (NF-kappa B) signaling in the skin. The therapeutic effects were associated with a significant increase in CD4(+)forkhead box protein 3 (FoxP3)(+) regulatory T cell (T-reg) frequency in the spleen and lymph nodes as well as FoxP3-positive staining in the skin lesion. Conversely, depletion of CD4(+)CD25(+) T-regs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL-17A(+)CD4(+) T cells in the spleen and lymph nodes of IMQ-induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future.