Abstract: OBJECTIVE To analyze the levels of thrombospondin-1 (TSP-1), high mobility group box 1 (HMGB1) and pentraxin 3 (PTX3) of the children with Mycoplasma pneumoniae pneumonia (MPP) and observe their association with M.pneumoniae deoxyribonucleic acid (DNA). METHODS A total of 135 children with MPP who were treated in Xuchang Maternity and Child Health Hospital from Jan 2020 to Jul 2022 were assigned as the study group (77 mild cases, 58 severe cases). Meanwhile, 147 children who received physical examination in the hospital were chosen as the control group. The levels of serum TSP-1, HMGB1 and PTX3 were detected. The levels of serum TSP-1, HMGB1 and PTX3 as well as the M.pneumoniae DNA level in bronchoalveolar lavage fluid (BALF) were observed and compared among the children with different illness condition and courses. RESULTS The levels of serum TSP-1, HMGB-1 and PTX-3 of the study group were higher than those of the control group (P＜0.05). The levels of serum TSP-1, HMGB1 and PTX3 as well as the level of bronchoalveolar lavage M.pneumoniae DNA of the severe children were higher than those of the mild children during the acute stage and recovery stage (P<0.05). The levels of serum TSP-1, HMGB1 and PTX3 as well as the level of bronchoalveolar lavage M.pneumoniae DNA of the mild, severe children were higher during the acute stage than during the recovery stage (P<0.05). Pearson correlation analysis showed that the serum TSP-1, HMGB1 and PTX3 levels were positively correlated with the M.pneumoniae DNA level. Spearman correlation analysis indicated that the serum TSP-1, HMGB1 and PTX3 were positively correlated with severity of disease. CONCLUSION The levels of serum TSP-1, HMGB1 and PTX3 of the children with MPP are elevated and are positively correlated with the severity of disease and the M.pneumoniae DNA level, which can be used as new targets for clinical diagnosis and treatment of the children with MPP.