Background: Psoriasis vulgaris is a common chronic immune-mediated skin disease associated with dysregulated inflammation and a number of comorbidities including diabetes, obesity, and metabolic dysfunction. Interlukin-17A (IL-17A) is highly differentially expressed in psoriatic skin lesions and plays a pivotal role in psoriasis pathogenesis. on the other hand, an important regulatory mechanism implicated in lipid metabolism is sterol regulatory element-binding protein 2 (SREBP2). Aim: The study aimed to evaluate the skin lesions expression of SREBP2, its relation to IL-17A expression and the impact of NB-UVB phototherapy on both in patients with psoriasis vulgaris. Methods: This case-control study included 40 participants (20 patients with psoriasis vulgaris and 20 healthy controls). Tissue biopsies were taken from psoriatic lesions before and after 20 sessions of narrow-band UVB phototherapy. Immunohistochemical staining was performed to assess IL-17A and SREBP2 expression scores. PASI score and metabolic parameters were also evaluated. Results: Before treatment, psoriasis patients had significantly lower SREBP2 expression (mean: 0.75 ± 0.64) compared to controls (mean: 2.4 ± 1.14, p < 0.001), and markedly higher IL-17A expression (mean: 2.6 ± 0.99 vs 0 in controls, p < 0.001). Following phototherapy, SREBP2 expression significantly increased (mean: 1.45 ± 1.36, p = 0.014), while IL-17A expression significantly decreased (mean: 1.75 ± 1.29, p = 0.003). PASI score dropped significantly (from 27.36 ± 10.52 to 14.18 ± 9.81, p < 0.001). IL-17A expression correlated negatively with PASI after treatment (p = 0.002). Conclusion: NB-UVB phototherapy effectively reduces disease activity in psoriasis, downregulating IL-17A and upregulating SREBP2 expression. IL-17A may serve as a predictive biomarker of therapeutic effect of NB-UVB, while SREBP2 may reflect NB-UVB beneficial metabolic restoration in psoriasis vulgaris patients.