Objective: To explore the synergistic therapeutic effect and mechanism of narrow band ultraviolet B (NB-UVB) phototherapy combined with levocetirizine hydrochloride in the management of pruritus in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 136 T2DM patients complicated with pruritus were enrolled as research subjects. They were assigned into two groups according to different treatment options, with 68 cases in each group. The monotherapy group received oral levocetirizine hydrochloride alone, whereas the combination group was administered NB-UVB phototherapy plus levocetirizine hydrochloride. Both groups underwent a 4-week treatment course. Before and after the intervention, the pruritus symptom score, skin lesion score, and quality of life score were assessed for all patients. Meanwhile, the levels of peripheral blood T lymphocyte subsets in patients were detected. The overall therapeutic efficacy of the two groups was also compared and analyzed. Results: The total effective rate of the combination group was higher than that of the monotherapy group (P < 0.05). After 4 weeks of treatment, the pruritus symptom score and skin lesion score in the combination group were lower than those in the monotherapy group (P < 0.05), while the quality of life score was higher in the combination group (P < 0.05). In terms of immune indicators, the levels of CD3+, CD4+ T lymphocytes and the CD4+/CD8+ ratio in peripheral blood in the combination group were higher than those in the monotherapy group (P < 0.05). Conclusion: NB-UVB phototherapy combined with levocetirizine hydrochloride can effectively alleviate pruritus symptoms and ameliorate skin lesions in T2DM patients with pruritus. More importantly, this combined regimen can regulate the disordered peripheral blood T lymphocyte subsets, improve the body's immune regulation, and thus achieve a better clinical therapeutic effect than single levocetirizine hydrochloride treatment.