BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition whose origins remain unclear. Existing epidemiological evidence suggests that inflammation and immune factors play pivotal roles in the onset and progression of AD. However, previous research on the connection between immune inflammation and AD has yielded inconclusive results. METHODS: To evaluate the causal relationship between immunological characteristics and AD, this study employed a bidirectional, two-sample Mendelian randomization (MR) approach. We utilized large-scale, publicly available genome-wide association studies to investigate the causal associations between 731 immunological feature cells and the risk of AD. RESULTS: Significant associations were identified between six immune phenotypes and AD risk: increased Basophil %CD33dim HLA DR-CD66b-, CD25 on IgD+ CD24+, CD40 on monocytes, HLA DR on CD14+ CD16-monocytes, HLA DR on CD14+monocytes correlated with higher AD risk, while elevated CD3 on CD4 Treg was linked to lower risk. Reverse MR analysis revealed AD as a risk factor for IgD+ CD38br AC and IgD+ CD38br %B cell, but a protective factor against CD20 on IgD+ CD38- naive and CD8 on NKT. CONCLUSION: Our findings elucidate the intricate interplay between immune cells and AD, informing future research into AD pathophysiology and therapeutics.