Exposure to low or moderate doses of lipopolysaccharides (LPS) renders the host tolerance to a subsequent lethal dose of LPS, which is termed as endotoxin tolerance. It is characterized as the decrease in production of pro-inflammatory cytokines and the increase in production of anti-inflammatory mediators in response to a second LPS challenge. The alteration of cytokine profile protects LPS-primed hosts against a normally lethal dose of subsequent LPS challenge. Nevertheless, whether other environmental factors also trigger endotoxin tolerance remains unclear. Both epidemiologic and experimental studies have provided a link between particulate matter and human health. Here, we speculated on the effect of fine particles priming on endotoxin tolerance in a mouse model.