【Abstract】Objective To investigate the role and the mechanism of zinc finger protein A20 (A20) on LPS-induced inflammation in cultured peritoneal mesothelial cells from Sprague-Dawley rats (RPMCs).  Method The second passage of cultured RPMCs were used in the study and randomly assigned into control group, LPS group, A20 plasmid transfection group, and parental plasmid transfection group. RPMCs were transfected with pGEM-T-easy-A20 plasmid using liposome for 12 hours, and were then stimulated with LPS. The cells and cell supernatant were harvested at different time after LPS stimulation. TLR4, p-IkBαand IkBα expressions in cells were determined by western blotting, and IL-18 in cell supernatant was determined by ELISA. Results In the A20 plasmid transfection group after LPS stimulation for 8h, the change of TLR4 expression was insignificant as compared with that in the control group (P=0.223), but was statistically different as compared with that in the LPS group and the parental plasmid transfection group (P=0.003 and 0.002, respectively). In the A20 plasmid transfection group after LPS stimulation for 1 h, p-IkBα expression changed insignificantly. The change of p-IkBα/IkBα ratio was insignificant as compared with that in the control group (p=0.553), but was statistically different as compared with that in the LPS group and parental plasmid transfection group (p=0.001 and 0.001, respectively). In A20 plasmid transfection group after LPS stimulation for 12 h, IL-18 secretion was higher (479.12±85.79 pg/ml) than that in the control group (274.34±47.21 pg/ml, P=0.012), but was lower than that in the LPS group (1049.45±185.01 pg/ml, P=0.011) and in the parental plasmid transfection group (1028.77±192.90 pg/ml, P=0.015).  Conclusions A20 inhibits the LPS induced inflammation in cultured RPMCs probably through negative regulation to several relevant proteins in the LPS signaling pathway.