Objective To develop a model that could copy the pathological development of psoriasis, the triple-transgenic mice that harboring Plasminogen activator, urokinase (PLAU),PLAU receptor (PLAUR) and signal transducer and activator of transcription 3 (STAT3) were generated. They are the important genes involved in the pathological development of psoriasis. Methods The transgenic plasmid was constructed by insertion of the PLAU, PLAUR and STAT3 into the downstream bovine keratin 5 promoter respectively. The transgenic mouse was produced by microinjection and the genotyping was detected by PCR. The expression level of the transgenic gene was determined by Western blotting. The pathological changes were observed by HE staining. Results One mouse line was selected with over expression of the PLAU, PLAUR and STAT3 in the tissue of skin. The transgenic mice showed decreased dermal layer, a hyperkeratinized cuticular layer and increased stratum spinosum. The number of hair follicle was reduced and developed abnormally in the transgenic mice. The Munro abscess in the dermal layer and the increased inflammatory cell infiltrates in dermal layer were also observed in the transgenic mice. Conclusions A transgenic mouse line was produced and passage stably, which expressed the PLAU, PLAUR and STAT3 in the tissue of skin and developed the psoriasis progressively. All of our results suggested that the transgenic mice were a useful animal model for psoriasis.