Psoriasis is a common and chronic skin disease associated with both genetic and environmental risk factors. Certain microorganisms could induce or exacerbate psoriasis through activation of keratinocyte TLRs (innate immunity). Toll-like receptors are pattern recognition receptors for conserved molecular patterns of pathogenic microorganisms. When TLR are activated by ligand exposure, TLR may trigger a Myeloid Differentiation Factor 88 (MyD 88) dependent pathway, which end by modulating the expression of many immune response genes.The study included 30 psoriatic patients (plaque type) and 30 controls, patients received 24 sessions of phototherapy (PUVA).Skin biopsies was taken from all the patients(before and after PUVA) and controls and was assessed for TLR 2,4 and MyD88 by PCR. Results showed significant difference between cases and controls as regards TLR2, TLR4 and MYD88, in addition a significant decrease in all the three studied parameters in patients after phototherapy. TLR2, TLR4 and MYD88 may play a role in the pathogenesis of psoriasis. Decrease in the level of these parameters after PUVA may be one of the therapeutic mechanisms of PUVA in psoriasis.