Abstract: Pseudomonas aeruginosa (PA) is a kind of opportunistic pathogen which can cause a wide range of serious infections clinically.These infections are often associated with the formation of biofilm, and are difficult to treat due to the complexity of mechanisms.Some studies have showed that genotype and phenotype of biofilm PA will change, and biofilm PA will aggregate together and secrete extracellular polymeric substance.Therefore, innate immune system could not recognize the camouflaged antigens.Besides, biofilm PA can secrete a variety of virulent factors to hamper the function of innate immune system.This article introduces the main chronic infection caused by PA biofilm and the relationship between biofilm PA and natural innate immune system.