Exocarpium Citri Grandis (ECG) is a famous traditional Chinese medicine, which has been commonly used to alleviate cough and phlegm for more than several hundred years, and total flavonoids are the main effective components of this medicine. This study investigated the effects of total flavonoids from ECG (TFECG) on pulmonary inflammation and oxidative stress induced by PM 2.5 in mice. Model mice received an intratracheal instillation of PM 2.5 (10 mg/mL) once at day 0. Bronchoalveolar lavage fluid (BALF) was collected after 72 hr to measure the total number of white blood cell (WBC), neutrophils (NEUT), lymphocytes (LYMPH), and monocytes (MONO). The levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18) in BALF were quantified by using enzyme-linked immunosorbent assay kits. Lung tissues were used to determine the contents of total protein (TP), malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), oxidized glutathione (GSSG) and the activities of superoxide dismutase (SOD), lactate dehydrogenase (LDH), Glutathione Peroxidase (GSH-Px), and inducible nitric oxide synthase (iNOS). We found that TFECG significantly inhibited PM 2.5 -stimulated overproduction of TNF-α, IL-1β, IL-6, and IL-18 and increased the numbers of WBC, NEUT, LYMPH, and MONO in BALF. TFECG observably relieved the PM 2.5 -induced increases in the contents of TP, MDA, and NO, and the activities of LDH and iNOS. TFECG also alleviated PM 2.5 -induced decreases in the activities of iNOS and GSH-Px as well as GSH/GSSG ratio. The results indicate that TFECG has anti-inflammatory and antioxidant activities, which may potentially contribute to the treatment of PM 2.5 -induced lung injury.Practical Application: Exocarpium Citri Grandis (ECG) is rich in flavonoids, which are beneficial to improve antiinflammation and antioxidant capacity. We proved that total flavonoids of ECG had a positive therapeutic effect on PM 2.5 -induced lung injury, which expands the potential applications of ECG in the dietary supplement industries.