Epidemiological studies have found that individuals with diabetes mellitus (DM) display an increased susceptibility for adverse cardiovascular outcomes when exposed to air pollution. This study was conducted to explore the potential mechanism linking ambient fine particles (PM 2.5 ) and heart injury in a Type 2 DM (T2DM) animal model. The KKay mouse, an animal model of T2DM, was exposed to concentrated ambient PM 2.5 or filtered air for 8weeks via a versatile aerosol exposure and concentrator system. Simultaneously, an inhibitor of IκB kinase-2 (IKK-â) (IMD-0354), which is a blocker of nuclear factor κB (NF-κB) nuclear translocation, was administrated by intracerebroventricular injection (ICV) to regulate the NF-êB pathway. The results showed that ambient PM 2.5 induced the increase of, NF-êB, cyclooxygenase-2 (COX-2) and mitogen activated protein kinase (MAPK) expression in cardiac tissue, and that IMD-0354 could alleviate the inflammatory injury. The results suggested that the NF-êB pathway plays an important role in mediating the PM 2.5 -induced cardiovascular injury in the T2DM model. Inhibiting NFκB may be a therapeutic option in air-pollution-exacerbated cardiovascular injury in diabetes mellitus.