Background: Chronic actinic dermatitis (CAD) is an immune-mediated photodermatosis characterized by a high eosinophil count and total immunoglobulin E (IgE) in the peripheral blood of patients. At present, however, the reasons for their elevation remain unclear.Objective: The current study aimed to detect changes in inflammatory cytokines in CAD and explore their role in this disease.Methods: Enzyme-linked immunosorbent assay and Luminex assay were conducted to measure inflammatory factor levels. Immunohistochemical analysis and quantitative real-time polymerase chain reaction were performed to evaluate the expression levels of interleukin-36? (IL-36?), IL-8, chemokine (C-C motif) ligand 17 (CCL17), and CCL18. CCK8 kits were used to assess cell proliferation. Immunofluorescence was used to detect nuclear factor ?B (NF-?B) p65 nuclear translocation. Western blot analysis was performed to detect the protein expression level of phosphorylated NF-?B (p-NF-?B) p65. Hematoxylin and eosin and Masson trichrome staining were applied to observe histological changes in a chronic photo-damaged mouse model.Results: Eosinophils, total IgE, IL-36?, IL-8, tumor necrosis factor a, CCL17, and CCL18 were elevated in CAD. Of note, IL-36? promoted the proliferation of eosinophilic cells (EOL-1) and the production of IgE in peripheral blood mononuclear cells. IL-36? also promoted the production of IL-8 and CCL18 in immortalized human keratinocytes (HaCaT cells), while ultraviolet radiation (UVR)-induced IL-36? via activation of the NF-?B signaling pathway.Conclusions: IL-36? was involved in the pathogenesis of CAD and UVR contributed to the production of IL-36?, which may provide a novel therapeutic target for CAD.