This study evaluated the anti-inflammatory effect of epicatechin (EC) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) of tracheal installation in BALB/c mice. It was observed that EC could alleviate not only the histopathological changes but also decrease the wet/dry weight (W/D) ratio of lung tissues. It also suppressed the release of IL-1β, IL-6, and TNF-α in serum, bronchoalveolar lavage fluid (BALF), and lung tissues, respectively. A quantitative realtime PCR-based study further indicated that EC also inhibited the levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA in lung tissues. In addition, the Western blot report suggested that EC was closely involved in the inhibition of phosphorylation of ERK, JNK, p38, p65, and IκB in mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathway. These results provide an experimental and theoretical basis for treating pulmonary inflammation by EC.