Fine particulate matter (PM2.5) is a significant environmental pollutant responsible for a number of human diseases. Ginsenoside Rg1 (Rg1) is likely to have the potential to relieve PM2.5-induced cell injury. The present study is designed to preliminarily observe the harmful effect of PM2.5 and the protective effect of Rg1 against PM2.5 on human A549 lung epithelial cells in vitro. The cytotoxic effects of the PM2.5 or Rg1 on A549 cells were measured by means of cell viability, and then exposure concentration of PM2.5 and pretreatment concentration of Rg1 used in the following assays were established. The A549 cells were pretreated with Rg1 for 1 h and then exposed to PM2.5 for 24 h. The levels of lactate dehydrogenase (LDH) in the cell culture supernatant and malondialdehyde (MDA) within the cells were assayed. The present results revealed that 200-1,200 g/ml of PM2.5 decreased the viability of A549 cells significantly in a concentration-dependent manner; however, 50-400 g/ml of Rg1 had no significant effect. Pretreatment with 100, 200 or 400 g/ml Rg1 significantly diminished the 200 g/ml PM2.5-induced A549 cell viability and decreased LDH leakage and MDA generation in a concentration-dependent manner. These results indicated that PM2.5 induced cell injury and Rg1, antagonized PM2.5-induced cell injury to a certain extent.