Updated project metadata. Yangyinqingfei Decoction (YYQFD), a traditional Chinese prescription, is well known in the treatment of diphtheria and lung-related diseases in clinic. However, the underlying mechanism how to treat lung-related diseases remains unclear. In the present study, the intervention effect of YYQFD on PM2.5-induced lung injury mice and its potential mechanism were investigated by metabolomics and proteomic techniques. The results showed that YYQFD could significantly improve pulmonary functions, relieve lung injury, as well as reduce IL-6, TNF-α and MDA, and increase SOD levels in serum and BALF of PM2.5-induced lung injury mice. Furthermore, the protein-metabolite joint analysis presented that YYQFD regulated the pathways of arachidonic acid metabolism, linoleic acid metabolism, and biosynthesis of unsaturated fatty acids with significantly down-regulating arachidonic acid, 20-HETE, prostaglandin E2, lecithin, linoleic acid, α-linolenic acid, eicosatetraenoic acid, and γ-linolenic acid, and up-regulating PTGES2, GPX2 and CBR3 protein expressions in lung tissue. A regulatory metabolic network map was further constructed, which provide us a better understanding about the role of YYQFD on PM2.5-induced lung injury mice and new insight into YYQFD application for the treatment of lung-related diseases.