OBJECTIVE Hypericin,a powerful naturally photosensitizer in photodynamic therapy(PDT),is suitable for treating skin diseases involving excess capillary proliferation.In the present study,we aimed to evaluate the skin penetrability of a topically applied hypericin,expecting reducing the risk of prolonged skin photosensitivity,which often occurs after systemic administration.METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers.In vivo studies,fluorescence microscopy was performed to examine the distribution of hypericin in the skin,macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment.Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin.RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most.The results of in vivo assays revealed that hypericin penetrated nude mice skin,spread to the dermis,and resulted in obvious photosensitivity reaction on the dermal capillaries.Moreover,skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin 7 d after hypericin-PDT treatment.CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases. OBJECTIVE Hypericin, a powerful naturally photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. The present study, we aimed to evaluate the skin penetrability of a topically applied hypericin, expecting reducing the risk of prolonged skin photosensitivity, which often occurs after systemic administration. METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers. vivo studies, fluorescence microscopy was performed to examine the distribution of hypericin in the skin, macroscopic and microscopic analyzes were also carried to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin .RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mice skin, spread to the dermis, and resulted in photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin for 7 days after hypericin-PDT treatment. CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases.