Background IL-4 and IL-13, pivotal components of type 2 immunity, have been implicated in inducing trained immunity in myeloid cells. However, the precise inflammatory response of monocytes in individuals with type 2 immune disorders remains uncertain. Objective To investigate the nuanced inflammatory response of monocytes in patients with type 2 immune disorders, specifically atopic dermatitis and urticaria, upon exposure to LPS stimulation. Methods We collected peripheral blood mononuclear cells (PBMCs) from patients diagnosed with atopic dermatitis and urticaria. Monocytes were isolated from PBMCs and subjected to targeted LPS stimulation. RNA extraction followed by RNA-seq and ATAC-seq analyses were conducted to elucidate molecular responses. Results Monocytes from patients with type 2 immune disorders exhibited an augmented inflammatory response upon LPS stimulation. RNA-seq analysis demonstrated significant upregulation of inflammatory cytokines, including IL-6, IL-12, and IL-1b. Moreover, there was a conspicuous enrichment of signaling pathways associated with inflammation. ATAC sequencing revealed heightened chromatin accessibility in patient monocytes, particularly in the promoter regions of inflammatory genes. Conclusion Our findings unveil an intensified pro-inflammatory response in monocytes following LPS stimulation in type 2 immune disorders such as atopic dermatitis and urticaria. The comprehensive RNA and chromatin analyses underscore the pivotal role of type 2 immune responses in shaping the epigenetically defined inflammatory phenotypes of peripheral monocytes.