Epidemiological studies have shown that exposure to diesel exhaust particles (DEP) is associated with metabolic diseases. We used mice with glucose intolerance and nonalcoholic fatty liver disease (NAFLD) caused by a high-fat, high-sucrose diet (HFHSD), which mimics a Western diet, to investigate the mechanism of metabolic diseases exacerbation via changes in innate immunity in the lungs by airway exposure to DEP. Six-week-old C57BL6/J male mice were fed HFHSD, and DEP was administered endotracheally once a week for eight weeks. Chronic exposure to DEP in HFHSD-fed mice increased inflammatory cells involved in innate immunity, such as type1 innate lymphoid cells (ILC1s), ILC2s, ILC3s, and M1 macrophages in the lungs and raised local inflammatory cytokine levels. This inflammation spread throughout the body, suggesting the association with the progression of NAFLD via increased inflammatory cells involved in innate immunity, such as ILC1s, ILC3s, M1 macrophages, and natural killer cells in the liver, and inflammatory cytokine levels in the liver which in turn exacerbated glucose intolerance. These findings contribute to a better understanding of the role of innate immunity in air pollution-related systemic diseases, especially metabolic diseases. Disclosure Y.Hasegawa: None. T.Okamura: Research Support; Yamada Bee Company, Inc. M.Hamaguchi: Research Support; Yamada Bee Company, Inc.. M.Fukui: None. H.Takano: None. Funding Japan Science and Technology Agency (JPMJCR19H3)