Abstract: OBJECTIVE To explore the intervention effect of regulating Toll receptor 4 (TLR4) on rat model with pulmonary Pseudomonas aeruginosa infection and observe the action mechanisms. METHODS Totally 150 rats were enrolled in the study, 30 of which were assigned as the blank group, the rest of 120 rats were established the models of pulmonary P.aeruginosa infection, 113 rats that were successfully established the models were divided into the model group with 37 rats, the up-regulated TLR4 group with 38 rats and the down-regulated TLR4 group with 38 rats.10 μl of TLR4-overexpressed lentivirus suspension and TLR4-silenced lentivirus suspension were respectively injected into the stomach of rats in the up-regulated TLR4 group and the down-regulated TLR4 group.The same dose of normal saline was injected into the stomach of rats in the blank group and the model group.The pathological characteristics of lungs of the rats were observed after the injection for 2 weeks.The changes of lung tissue inflammatory factors and oxidative stress indexes as well as the relative expression levels of myeloid differentiation factor 88(Myd88)/nuclear factor-κB(NF-κB) signaling pathway proteins were observed. RESULTS The relative expression level of TLR4 of the model group, the up-regulated TLR4 group and the down-regulated TLR4 group was higher than that of the blank group(P＜0.05), indicating a successful transfection.The levels of inflammatory factors interleukin (IL)-6, macrophage inflammatory protein-2 (MIP-2) and IL-8 were elevated in the TLR4 up-regulated lung tissues(P＜0.05); the levels of oxidative stress indexes malondialdehyde (MDA) and myeloperoxidase (MPO) were elevated; the total antioxidant capacity (T-AOC) was reduced (P＜0.05).The relative expression levels of Myd88 and NF-κB proteins were elevated(P＜0.05). CONCLUSION The down-regulation of TLR4 may alleviate the inflammatory response of the rats with pulmonary P.aeruginosa infection and improve the status of oxidative stress, and the action mechanisms may be associated with the inhibition of Myd88/NF-κB signaling pathways.