Objective To study the effect of Liangxue Tuizi Formula(LXTZF) on reactive oxygen species(ROS)-mediated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation in Henoch-Sch?nlein purpura rats, and to explore the possible mechanism of Liangxue Tuizi Formula in the treatment of HSP. Methods 24 rats were randomly divided into 4 groups: blank group, model group, LXTZF group and Compound Glycyrrhizin (CG) group. Except the blank group, the rat model of a Henoch-Sch?nlein purpura was established by heat drug combined with egg albumin (OVA). After successful modeling, LXTZF group was given LXTZF solution 7.47 g·kg-1, CG group was given CG solution 13.5 mg·kg-1 by gavage, blank group and model group were given normal saline solution gavage once a day for 4 weeks. Samples were collected 8 hours after the last gavage. Hematoxylin-eosin staining (HE) was used to observe the skin histopathologic changes. Serum Interleukin-18 (IL-18) and Interleukin-1β (IL-1β) levels were detected by enzyme-linked immunosorbent assay (ELISA). The changes of ROS levels in the skin of rats were detected by immunofluorescence. Real-time quantitative PCR (RT-qPCR), immunohistochemical and western blot methods were used to detect Apoptosis-associated speckle-like protein (ASC), NLRP3, Cysteinyl Aspartate-Specific Protease-1 (Caspase-1) gene mRNA and protein expression in rat skin. Results Compared with the blank group, the skin pathology of the model group showed obvious inflammatory cell infiltration. Serum IL-18 and IL-1β levels were significantly increased (P<0.05), skin ROS levels were significantly increased (P<0.05), and skin ASC, NLRP3, Caspase-1 mRNA and protein expression levels were significantly increased (P<0.05). Compared with the model group, the infiltration of inflammatory cells in the skin tissues of rats in the LXTZF group and the CG group was alleviated, the levels of serum IL-18 and IL-1β in the CG group and LXTZF group were significantly decreased (P<0.05). The level of ROS in the skin was significantly decreased (P<0.05), and the mRNA and protein expression levels of ASC, NLRP3 and Caspase-1 in the skin were significantly decreased (P<0.05). Conclusion The mechanism of Liangxue Tuizi Formula in the treatment of Henoch-Sch?nlein purpura may be related to the inhibition of ROS-mediated NLRP3 inflammasome activation.