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Abstract Henoch-Schonlein purpura nephritis (HSPN) is a systemic vascular inflammatory disease. Huanglian Decoction (HLD) ameliorates renal injury in nephritis; however, the mechanism of action of HLD on HSPN has not been investigated. This study aimed to investigate the protective mechanism of HLD treatment in HSPN. The effects of HLD on HSPN biochemical indices, kidney injury and NF-κB/NLRP3 signaling pathway were analyzed by biochemical analysis, ELISA, HE and PAS staining, immunohistochemistry, immunofluorescence, and Western Blot. In addition, the effects of HLD on HSPN cells were analyzed. We found that HLD treatment significantly reduced renal tissue damage, decreased the levels of IL-17, IL-18, TNF-α, and IL-1β, and increased the levels of TP and ALB in HSPN mice. It also inhibited the deposition of IgA, IgG, and C3 in kidney tissues and significantly decreased the expression of IκBα, p-IκBα, NLRP3, caspase-1, and IL-1β in kidney tissues and cells. In addition, PMA treatment inhibited the above-mentioned effects of HLD. These results suggested that HLD attenuates renal injury, IgA deposition, and inflammation in HSPN mice and its mechanism of action may be related to the inhibition of the NF-κB/NLRP3 pathway. HenochSchonlein Henoch Schonlein (HSPN disease (HLD however investigated indices NFκB/NLRP3 NFκBNLRP3 NFκBNLRP NF κB/NLRP3 κB NLRP3 NLRP NF-κB/NLRP analysis ELISA staining immunohistochemistry immunofluorescence Blot addition damage IL17, IL17 IL 17, 17 IL-17 IL18, IL18 18, 18 IL-18 TNFα, TNFα TNF α, α TNF-α IL1β, IL1β ILβ 1β, 1β β IgG C IκBα pIκBα, pIκBα p p-IκBα caspase1, caspase1 caspase 1, 1 caspase-1 abovementioned above mentioned NFκB NFκB/NLRP κBNLRP3 κBNLRP κB/NLRP IL1 IL-1 caspase- IL-