Objective This study aimed to observe the clinical efficacy of 308 nm excimer laser combined with tacrolimus in the treatment of vitiligo and its effect on T lymphocyte subsets. Methods A total of 121 cases of vitiligo patients admitted to our hospital from October 2019 to October 2022 were selected. They were randomly divided into a control group (treated with tacrolimus，58 cases) and an observation group (treated with 308 nm excimer laser + tacrolimus，63 cases). The clinical efficacy，T lymphocyte subsets (CD4+， CD8+，CD4+/CD8+)，serological indicators [monocyte chemotactic protein-1 (MCP-1)，sICAM-1]，Inflammatory factors [Interleukin-17 (IL-17)，IL-23]，and adverse reactions were compared between the two groups . Results The total clinical effective rate of the observa⁃ tion group was higher than that of the control group (P < 0.05). After intervention，the levels of CD4+ and CD4+/CD8+ increased，while the level of CD8+ decreased in both groups. The levels of CD4+ and CD4+/CD8+ in the observation group were significantly higher，and the level of CD8+ was lower than those in the control group (P < 0.05). After intervention，the levels of MCP-1 and sICAM-1 in the two groups were significantly decreased，and the levels of MCP-1 and sICAM-1 in the observation group were lower than those in the con⁃ trol group (P < 0.05). After intervention，the levels of IL-17 and IL-23 in both groups significantly decreased，and the levels of IL-17 and IL-23 in the observation group were lower than those in the control group (P < 0.05). There was no statistically significant differ⁃ ence in adverse reactions between the two groups (P > 0.05). Conclusion 308 nm excimer laser combined with tacrolimus had better clinical efficacy than tacrolimus alone in the treatment of vitiligo patients. Its mechanism might be related to the influence of T lympho⁃ cyte subsets，sICAM-1 and IL-23 expression levels. Moreover，it was relatively safe and held great importance in improving the clinical efficacy of vitiligo.