<p>Psoriasis is a chronic, immune-mediated inflammatory disorder in which persistent T-cell activation by antigen-presenting cells (APCs), alongside defects in immune tolerance, contributes to disease development, similar to other autoimmune conditions. Programmed death-1 (PD-1) is an inhibitory co-receptor that modulates inflammation and maintains peripheral immune tolerance. Dysfunction of the PD-1/PD-L1 pathway is believed to play a significant role in the pathogenesis of numerous immune-mediated diseases. The objective of this study was to assess the expression of programmed death-ligand 1 (PD-L1) in psoriasis by evaluating its immunohistochemical (IHC) expression in lesional skin of psoriatic patients. This prospective case–control study included 30 skin biopsies from patients with plaque psoriasis and 20 biopsies from age- and sex-matched healthy individuals who served as the control group. Immunohistochemical staining using a monoclonal mouse anti–PD-L1 antibody (clone 22C3) was performed on skin biopsy specimens obtained from both the patient and control groups. There was a highly statistically significant difference in PD-L1 expression between the two groups (<i>P</i> &lt; 0.001). In the patient group, 30% of specimens showed low expression and 70% showed high expression, compared with 80% low expression and 20% high expression in the control group. A strong, statistically significant inverse correlation was observed between the number of PD-L1–positive immune cells and PASI scores (<i>P</i> &lt; 0.001, <i>r</i> = -0.77). Furthermore, the number of PD-L1(+) immune cells demonstrated a statistically significant negative correlation with disease duration (<i>P</i> = 0.02, <i>r</i> = -0.42). In conclusion, PD-L1 is significantly upregulated in dermal immune cells of psoriatic skin, correlating inversely with disease severity and duration. This suggests a compensatory immunoregulatory role, warranting further mechanistic studies to confirm its therapeutic potential.</p>