Inflammatory-mediated reactions have been implicated as contributors in a number of dermatological disorders, including psoriasis. However, the potential of interleukin (IL)-32 and its isoforms to contribute to the pathogenesis of psoriasis remains unexplored. This study was undertaken to investigate the role of IL-32 and its isoforms IL-32α, IL-32β, IL-32γ, and IL-32δ in the peripheral blood of psoriatic patients. The majority of chronic plaque psoriatic patients showed elevated IL-32 mRNA levels in the peripheral blood mononuclear cells (PBMCs) as compared with the levels of IL-32 mRNA in PBMCs of healthy controls (p = 0.001). To further investigate the role of elevated levels of IL-32 in psoriatic patients, IL-32 isoforms mRNAs were determined. All tested isoforms IL-32α, IL-32β, IL-32γ, and IL-32δ were overexpressed in psoriatic patients PBMCs as compared with healthy controls' PBMCs (p < 0.05). IL-32α mRNA expression was also significantly higher as compared with all other isoforms of IL-32 in PBMCs of psoriatic patients (p < 0.001). In short, this is the first study that shows the role of IL-32 and its isoforms in the peripheral blood of psoriatic patients. Our novel findings support an association between elevated levels of IL-32 and psoriasis. The data also suggest that a major proinflammatory response of IL-32 may derive from IL-32α isoform in psoriasis.