Psoriasis is a common genetically determined inflammatory and proliferative disease of the skin. The cause of psoriasis is not fully understood, but it is believed to have a genetic component and local psoriatic changes can be triggered by multiple factors that cause insult to the skin. Various environmental factors have been suggested as aggravating to psoriasis including stress. Skin responds to environmental stressors via coordinated actions of the local neuroimmunoendocrine system. Although some of these responses involve opioid receptors, little is known about cutaneous proenkephalin (PENK) expression, its environmental regulation and alterations in pathology. It has been reported that Proenkephalin plays an important part in the immune reactions and exerts a proliferative effect in human keratinocytes. This study is performed to assess possible role of the proenkephalin in the pathogenesis of psoriasis in order to find new ways of investigation and new modalities of treatment. The results of our study have demonstrated that the level of proenkephalin in both serum and tissues of patients are significantly higher than those of controls. Proenkephalin or other neuropeptides may play a role in the pathogenesis of psoriasis and there are an interaction between the skin and the nervous system.