Objective : To investigate the effect of high concentration of Caerulomycin A (Cae A) on HK2 in renal tubular epithelial cells and to explore the role of cytoplasmic nucleotide⁃binding oligomerization domain⁃like receptor protein 3 (NLRP3) in this process. Methods : The effect of different concentrations of Cae A on the viability of HK2 cells was determined by MTT; the expression of kidney injury molecule (KIM⁃1) and NLRP3 was detected by real⁃time quantitative PCR , Western blot and immunofluorescence , while the effect of Cae A on the mRNA expression of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α was also measured by real⁃time quantitative PCR. HK2 cells were divided into control group , high concentration of Cae A group and high concentration of Cae A plus NLRP3 inhibitor CY⁃09 group , and the expression of KIM⁃1 and NLRP3 protein was detected by Western blot. Results : The results of MTT showed that high concentration of Cae A could inhibit HK2 cell viability. Real⁃time quantitative PCR , Western blot and immunofluorescence assays showed that high concentration of Cae A upregulated the expression of KIM⁃1 and NLRP3 , as well as the mRNA levels of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α , while CY⁃09 could down⁃regulate the expression of NLRP3 and KIM⁃1. Conclusion High concentration of Cae A significantly inhibited the viability of HK2 cells and induced damage and inflammatory response to HK2 with some nephrotoxicity that might be achieved via NLRP3 pathway.