Abstract. This study investigated the effect of Panax notoginseng saponins (PNS) on acute lung injury (ALI) induced by oleic acid (OA) and lipopolysaccharide (LPS). A total of 28 Wistar rats were divided into four groups: sham; sham + PNS; OA-LPS-induced ALI and ALI + PNS. Lung tissue histology, lung wet-to-dry (W/D) weight ratio, extravascular lung water (EVLW) and epithelial sodium channel α (αENaC) mRNA and protein expression were examined. In addition, levels of inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-10, as well as total leukocyte and neutrophil counts, were analyzed in rat bronchoalveolar lavage fluid (BALF) and serum. ALI + PNS rats were observed to exhibit significantly lower pulmonary parenchymal damage and EVLW compared with ALI rats. Furthermore, total leukocyte and neutrophil counts, and levels of inflammatory cytokines were significantly decreased following PNS administration in ALI rats. In addition, the decrease in αENaC mRNA and protein expression observed in the lung tissue of ALI rats was partially restored following PNS treatment. PNS treatment was demonstrated to ameliorate OA-LPS-induced ALI, potentially through restoration of αENaC mRNA and protein expression and through PNS-induced anti-inflammatory effects.