This comprehensive review was depicting the role of inflammatory mediators and HPA-axis involvement in the pathogenesis of psoriasis. The increased IL-23, IL13, IL-10 were aggravating factors in the itching process of psoriasis. Simultaneously, over-activity of the HPA-axis was also observed that was increasing CRH and α-MSH levels, which were implicated in the induction of itching process through various receptor-like CRHR1, MC1R, MC5R. This evidence concerns the gene MC5R and psoriasis.