Objective To observe the effects of Xiaohuang decoction (XHD) on anti-oxidative stress and macrophage activation in lungs of rats with dimethylnitrosamine (DMN) -induced liver fibrosis.Methods Liver fibrosis was induced in male Wistar rats by DMN injection, three days a week for four weeks and divided into two groups: untreated model group and XHD-treated group.XHD or distilled water was administered eight times a day for two weeks.All rats were sacrificed at the end of the 4th week and lung tissues harvested for analysis.Oxidative stress indicators [superoxide dismutase (SOD) , glutathione (GSH) , and malondialdehyde (MDA) ] in the lung were detected by biochemical assays.CD68 expression in the lung was detected by Western blot, immunohistochemistry, and real-time quantitative PCR.Results In the DMN-induced rats, SOD activity and GSH content had decreased remarkably after two weeks and was maintained at a low level state out to four weeks, but MDA content had increased after two weeks.XHD treatment significantly reduced the DMN-enhanced MDA content and notably increased the DMN-inhibited SOD activity and GSH content after four weeks.Immunohistochemical analysis of uninduced normal control rats revealed that CD68 was localized to the alveoli and weakly expressed.However, in DMN lung, the CD68 expression was strong after two weeks.XHD-treated DMN rats had weak CD68-positive staining in lung.Conclusion Oxidative stress and activation of macrophages occurred in the lung during DMN-induced hepatic fibrosis.XHD treatment inhibits oxidative stress and lung macrophage activation.