Psoriasis is an inflammatory skin disease characterized by the presence of whitish and scaly plaques, which can cover up to 90% of the body surface. These plaques result from the hyperproliferation and abnormal differentiation of keratinocytes. Dermopharmaceutical testing of new therapies is limited by healthy and pathological skin models, which are not closely enough mimicking their in vivo counterparts. In this study, we exploited percutaneous absorption and Ultra Performance Liquid Chromatography (UPLC) analyses in order to determine the metabolic capacity of our psoriatic skin model. Skin substitutes were reconstructed according to the self-assembly method and tested regarding their percutaneous absorption of a topical formulation of tazarotene, followed by UPLC analyses. Histological and immunofluorescence analyses confirmed both the healthy and psoriatic phenotypes. Results from percutaneous absorption showed a significant level of tazarotene metabolite (tazarotenic acid) when the formulation was applied over 24 h on the skin substitutes. The presence of tazarotenic acid in the dermis and the epidermis of healthy and psoriatic skin substitutes confirms the metabolic capacity of both skin models, and thereby their ability to screen new molecules with antipsoriatic potential. In conclusion, the present data suggest that our psoriatic skin model could possibly be used in clinic to screen in vitro responses of patient to a panel of drugs without having them experiencing the drawback of each drug.