The role of skullcapflavone II in pneumonia was investigated using lipopolysaccharide treated human lung fibroblasts WI-38 cells as a model. Lipopolysaccharide treatment led to decreased cell viability, increased cell apoptosis and inflammation. Exposure of these lipopolysaccharide-treated cells to skullcapflavone II resulted in amelioration of cytotoxic effects of the lipopolysaccharide. The reduced IκBα expression and enhanced p-IκBα and p-p65 in WI-38 cells caused by the lipopolysaccharide treatment were reversed by skullcapflavone II. In conclusion, skullcapflavone II exerts antiapoptotic and anti-inflammatory effects on lipopolysaccharide-induced WI-38 through inhibition of NF-κB pathway.