This protocol describes the generation of a skin humanized mouse model for psoriasis using bioengineering approaches. This method is relatively simple, highly reproducible and ensures the obtention of a large and homogenous number of engrafted animals bearing a portion of human skin with psoriatic phenotype. The technique can employ cells from skin biopsies and blood samples from non-related healthy human donors (allogeneic version), as well as skin and blood cells from psoriatic patients (autologous version). In both cases, the psoriatic phenotype was developed after intradermal administration of in vitro derived T1 lymphocytes along with Th17 recombinant cytokines, in conjunction with mild barrier disruption by tape-stripping. This skin-humanized model for psoriasis emerges as a powerful tool to study the mechanisms underlying the pathogenesis of the disease. More importantly, the feasibility of the system may allow the evaluation of different therapeutic compounds in an in vivo system, employing local and/or systemic administration.