Objective To investigate the expression of HMGB1, RAGE, and IL-6 in patients with Henoch-Schonlein purpura (HSP), and to explore their roles in the development of HSP. Methods A total of 80 patients diagnosed with Henoch-Schonlein purpura at the Affiliated Hospital of Chengde Medical University from January 2022 to July 2024 were selected as the research objects. According to the results of the urine examination, patients were split into renal purpura group and non-renal purpura group, and a health examination population in the same period were selected as the control group. The expression of HMGB1, RAGE, and IL-6 was detected by ELISA. Non-parametric test and binary logistic regression model were utilized to analyze the data, and the ROC curve was adopted to analyze the predictive value of indicators for renal purpura. Results The expression levels of HMGB1 and IL-6 were highest in the renal purpura group, and the non-renal purpura group was higher than the control group (P<0.05). The expression levels of RAGE showed little difference between the renal purpura group and the non-renal purpura group (P>0.05), with both groups being higher than the control group (P<0.05). Binary logistic regression analysis shows that the increase in HMGB1 and IL-6 is statistically significant in the occurrence of renal purpura. The ROC curve indicates that the rise in HMGB1 and IL-6 demonstrates significant clinical significance for the early assessment of kidney damage. Conclusion HMGB1, RAGE, and IL-6 may be involved in the occurrence and development of HSP. HMGB1 is expected to be a potential target for the treatment of HSP. The combined detection of HMGB1 and IL-6 has high clinical value for early evaluation of the occurrence of renal purpura.