Herein, we found that serum content of the triggering receptor expressed on myeloid cells-1 (TREM1) was increased, and positively correlated with Mycoplasma pneumoniae (MP)-DNA in children with MP infection. In this study, A549 cells, known as human lung epithelial cells, were co-cultured with 10 CCU/ml of MP to established in vitro model of MP infection. We studied the roles of TREM1 in inflammatory response of A549 cell by regulating the secretions of cytokine interleukin (IL)-8 and tumor necrosis factor (TNF)-α in cell culture supernatants. Moreover, transcriptional activity of nuclear factor kappa B (NF-кB) was assessed by measuring protein levels of NF-кB in the cytoplasm and nuclear. Our data suggested that sanguinarine chloride significantly decreased TREM1 expression, and alleviated inflammatory response of MP-infected A549 cells via preventing NF-кB nuclear translocation. To study the roles of TREM1 in inflammatory regulation in MP-infected A549 cells and the underlying mechanisms, we established TREM1 overexpression transfected A549 cells. PDTC was used for inhibiting NF-кB nuclear translocation. We found that TREM1 overexpression induced server inflammatory response of A549 cells. Besides, TREM1 overexpression attenuated anti-inflammatory effects of sanguinarine chloride in MP-infected cells. More importantly, pro-inflammatory effects of TREM1 overexpression was significantly reversed with additional PDTC treatment in MP-infected cells treated with sanguinarine chloride, suggesting that TREM1 was a pro-inflammatory factor via regulating NF-кB nuclear translocation in MP-infected A549 cells.