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Psoriasis is an immune-mediated chronic skin disease caused by immune system mistakes and overproduction of new skin cells.Itchy, plaque-like, scaly, painful and disfiguring skin lesions occur in the skin of psoriatic patients [1].Imiquimod (IMQ) is a TLR7/8 ligand and potent immune activator, which can induce and exacerbate psoriasis [2].The aim of this work is to compare the permeability differences of three transdermal marker drugs on IMQ-induced psoriasis like mouse skin and normal skin.Female C57/BL6 mouse was anesthetized using chloral hydrate and shaved.Then IMQ was applied on the skin for a few days to form the psoriatic skin.The psoriatic skin was confirmed using HE staining.Normal and psoriatic mouse skin was mounted on side by side transdermal diffusion cell (PermeGear, US) with the stratum corneum facing the donor part.Three widely used transdermal drug named Indomethacin (IM), idocaine (LD), and 5-fluorouracil (5-FU)with the log P of 4.25, 2.20 and-0.95 were selected as the model drugs.Supersaturated drug in isopropyl myristate was added in the donor cells while PBS (pH 7.4) was added in the acceptor cells.The system was maintained at 32 ℃ for 8 hours.Sample of 2 mL was withdrew and supplemented at predetermined intervals.After centrifugation, the sample was measured using HPLC and the penetration flux was calculated.The results of model establishment were shown in Fig.1.The psoriatic skin showed desquamation, erythema and epidermis thickening.Consistent with the appearance of skin photos, the hyperplasia of basal and suprabasal keratinocytes expressed in psoriatic skin in HE staining results.For in vitro penetration, the penetration flux of IM, LD and 5-FU through psoriatic skin was 2.06, 1.55 and 1.11 times higher to that of normal skin (Fig.2),which means higher speed penetration through psoriatic skin.And there is a proportional relation between the permeation enhancing effect and the value of log P.The pathological membrane of psoriasis showed higher effect on the transdermal agent with higher log P.This experiment indicated that the enhanced penetration ability of drugs with different lipophilicity across psoriatic skin should be considered in transdermal drug formulation design.