Background: Rhododendron brachycarpum has been used in a traditional oriental medicine for the treatment of skin diseases such as psoriasis and eczema. In human innate immune defense, TLR7 is highly expressed in some skin diseases, such as psoriasis. Objectives: In this study, we demonstrated whether rhododendrin isolated from Rhododendron brachycarpum could inhibit TLR7 signaling-mediated skin inflammation. We showed that TLR7 is expressed on the differentiated normal human epidermal keratinocytes induced by calcium, and rhododendrin could inhibit imiquimod-induced NF- B activation and the expression of TNF- , IL-6 in normal human epidermal keratinocytes. Methods: To explore the inhibitory effect of rhododendrin on skin inflammation in vivo, we pretreated the rhododendrin in mouse skin followed by imiquimod treatment. Results: The result showed that imiquimod-induced increase in skin thickness was inhibited in a dose-dependent manner by treatment with rhododendrin and major induced inflammatory cytokines and chemokines, such as IL-17, CCL20 and IL-6 were reduced by the treatment with rhododendrin. We also demonstrated that rhododendrin could inhibit IL-23-induced psoriasis-like skin inflammation. Conclusion: These results suggest that rhododendrin has an anti-inflammatory effect on the skin inflammation and imply that it has therapeutic potentials for the skin inflammatory diseases, such as psoriasis.