Background: Psoriasis is a common inflammatory T-cell mediated skin disorder. An early cellular event in the development of a psoriatic lesion is the influx of activated T-cells by chemokines into the affected skin. Various chemokines are synthesized in inlflamed skin. One of these chemokines is RANTES, which produced by epidermal keratinocytes. RANTES may contribute to Th1 dominant infiltration in psoriatic lesions.Th-1 cells in turn produce proinflammatory cytokines such as TNF-α, IL-1β or IFN-γ, which promote RANTES production by keratinocytes. Thus RANTES production in psoriatic lesions may amplify the inflammation in the lesions. The blockage of production of RANTES production by keratinocytes is the key therapeutic target for psoriasis.Aim of work: The aim of the present work is paving the way to understand the role of RANTES in the pathogenesis of psoriasis and the evaluation of RANTES in skin lesions of psoriasis before and after NB-UVB phototherapy.Patients and methods: The study included 25 patients of psoriasis vulgaris (plaque type) (10 males and 15 females) their ages ranged from 19 to 70 years old with a mean age of 44 + 16.60 years old. The patients received 24 session of NB-UVB. Skin biopsies were taken from the patients before and at the end of phototherapy. The biopsies will be subjected to molecular analysis by RNA extraction of RANTES gene then amplification of RANTES gene by real time PCR. Results: RQ RANTES mRNA expression was significantly reduced after treatment with NB-UVB phototherapy. A statistically significant negative correlation was found between pre-treatment RQ RANTES mRNA expression and both the post-treatment extents of body involvement and post-treatment PASI scores. Furthermore, we found a statistically significant negative correlation between dRQ RANTES mRNA expression (difference between of RQ RANTES mRNA expression before and after phototherapy) and PASI score after phototherapy. We found statistically significant negative correlations between pretreatment RQ RANTES mRNA expression and both initial response session number and total dose. Also statistically significant negative correlations were found between the dRQ RANTES mRNA expression and dose at initial response, as well as, total end of therapy NB-UVB dose. . Thus these results lead us to surmise that pretreatment RQ RANTES mRNA expression could be considered as a marker or indicator for clinical improvement and as an indicator or determinant for NB-UVB phototherapy efficacy. Conclusion: NB-UVB phototherapy has suppressive effect on the mRNA RANTES gene in the psoriatic lesions. So that it might be one of the modulatory effects of UVB irradiation on cutaneous inflammation in psoriasis. The blockage of production of RANTES is the key therapeutic target for NB-UVB phototherapy in psoriasis as we found that better clinical improvement and faster response to NB-UVB phototherapy in patients with higher RANTES mRNA expression pre-treatment.