Objective To investigate the relationship between serum midkine (MK), S100 Calcium Binding Protein A9 (S100A9), and Pentraxin 3 (PTX3) levels in children with Henoch-Schonlein purpura The relevance and diagnostic value of involvement. Methods A total of 118 children with Henoch-Schonlein purpura admitted to our hospital from March 2015 to March 2019 were included as the study group, and 118 healthy children with physical examination during the same period were included as the control group. Enzyme-linked immunosorbent assay was used to detect the expression of MK, S100A9, and PTX3 in the serum of the study group and the control group. The AUC analysis of receiver operating characteristic curve (ROC) was used to analyze the MK, S100A9, and PTX3 detection in allergic purpura Significance of diagnosis in children. Spearman correlation coefficient analysis of the correlation between serum levels of MK, S100A9, PTX3, and renal involvement in children with Henoch-Schonlein purpura. Results The expression levels of MK, S100A9, and PTX3 in the serum of children with Henoch-Schonlein purpura were significantly higher than those of healthy children (P＜0.05). The sensitivity of MKS100A9, and PTX3 in children with Henoch-Schonlein purpura and healthy children were 89.35%, 94.26%, and 90.18%, and the specificity was 86.32%, 94.21%, and 91.42%, respectively. The sensitivity of the combination of MK, S100A9, and PTX3 in serum for the diagnosis of Henoch-Schonlein purpura was 97.46%, the specificity was 87.28%, and the accuracy was 92.37%. The levels of MK, S100A9, and PTX3 in serum were positively correlated with renal involvement in children with Henoch-Schonlein purpura (P＜0.05). Conclusion The expression levels of MK, S100A9, and PTX3 in serum are positively correlated with renal involvement in children with Henoch-Schonlein purpura. The detection of their expression levels can be used as an important marker for the diagnosis of children with Henoch-Schonlein purpura.