〔Abstract〕 Objective To establish and characterize an inducible,CD4 + T cell-specific ablation mouse model (CD4-iDTR) using the Cre-loxP and diphtheria toxin receptor (DTR) systems, and to evaluate its depletion efficacy and specificity. Methods CD4-iDTR mice were generated through cross-breeding, with genotypes confirmed viaPCR-based screening. Mice were categorized into an untreated (control) group and a diphtheria toxin (DT) induction group. Flow cytometry was employed to compare the baseline distribution of CD4 + T cells between untreated CD4-iDTR and wild-type C57BL/6 mice.In the DT group, CD4 + T cell ablation was induced by subcutaneous DT administration. The depletion efficiency in skin tissues and skin-draining lymph nodes (sdLNs) was quantified at 24 h and 1 week post-injection. Furthermore, the proportions of neutrophils, macrophages, dendritic cells, and other CD11b + immune cell subsets in the skin were monitored to assess the model specificity. Results Genomic profiling confirmed the successful generation of the CD4-iDTR line. Under steady-state conditions, no significant differences were observed in the frequency or absolute number of CD4 + T cells in the skin and sdLNs between CD4-iDTR and C57BL/6 mice ( P>0.05). Following DT induction, the CD4 + T cell population in the skin exhibited decline within 24 h and 1 week ( P <0.05), whereas the CD4 + T cell counts in sdLNs remained stable. The percentages of cutaneous neutrophils, macrophages, and other CD11b +myeloid populations were not significantly altered following DT treatment ( P>0.05). Conclusion The CD4-iDTR mouse model is successfully established and bred, achieving efficient, specific, and inducible ablation of cutaneous CD4 + T cells without significant interference with the skin immune microenvironment. This model serves as an ideal experimental tool for investigating skin-specific immunological mechanisms.