Objective To explore the relationship between phosphatidylinositol 3-kinase ( PI 3-kinase) and psoriasis. Methods We constructed eukaryotic expression vector PcDNA 3-PI 3-kinase, by which digoxin-labeled RNA probe of PI 3-kinase was generated. After that, we detected the expressions of PI 3-kinase in the skins of twelve patients with plaque psoriasis and five normal subjects by dot blot, in situ hybridization and immunohistochemistry. Results The expression of PI 3-kinase mRNA and protein in psoriatic lesions increased obviously compared with that in normal skin. The expression of the PI 3-kinase gene conformed to the expression of its protein in psoriatic and normal human skins. Conclusions Over-expression of PI 3-kinase may be related to the hyperproliferation of psoriatic keratinocytes. Transfection of the anti-sense gene of PI 3-kinase into psoriatic keratinocytes might be a best way to elucidate the issue.