Diesel exhaust nanoparticles (DENPs) are gaseous exhaust and one component of particulate matter (PM) air pollution which is found to cause health hazards in humans. Quercetin is widely known for its antioxidant and antitoxic potential. We aimed todetect the protective effect of quercetin in DENP-induced cardio toxicity. Fifty Malealbino rats were divided into two groups,first group (ten rats) divided into two equal subgroups (one receive saline act as control and other receive quercetin,the second group (forty rats)divided equally into two subgroups (one was treated with repeated doses of DENPs [90µg/ rat and 180µg/ rat for 6 days intratracheally every two days] and other treated orally with quercetin (60 mg/kg B.Wt.) 1h prior to DENP exposure,DNA damagewas examined by measureserum8-hydroxydeoguanosine (8-OHdG) levels followed by histological and immunohistochemical studies for nuclear factor-kappa B(NF-κB) expression in heart tissues. Tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6) and serum level 8-Ohd Gare significantly higher in repeated doses of DENPs than the control group. Pretreatment with quercetin reduced significantly serum level 8-OhdGwhen compared to DENPs group.Cardiac myocytes disruption, vacuolation, inflammation and wide separation of its fibers in contrast to control group. Myocyteinflammations were significantly decreased with quercetin group compared with control group (decrease NF-κBimmunostaining). The present work yields experimentalevidence that quercetin can reduce oxidative DNA damage and inflammation induced by DENPs, so suggested that quercetin possible cardioprotective effect against DENPs.