This study aims to investigate the effect and mechanism of crocin (CRO) on diabetic kidney disease (DKD) from the perspective of epithelial-mesenchymal transition (EMT) and NLRP3 pathway.Sixty C57BL/6J mice were adaptively fed for one week and ten mice were selective as normal control group randomly.The remain mice received high-fat diet for eight weeks followed by streptozotocin (STZ) injection. After STZ modeling,the modeled mice were randomly divided into model group,NLRP3 inhibitor group (10 mg/kg,intraperitoneal injection),low-dose CRO group (5 mg/kg,gavage),middle-dose CRO group (10 mg/kg,gavage),high-dose CRO group (20 mg/kg,gavage).After eight weeks of treatment,24 h urine samples,blood samples and kidneys were collected for analysis and determination.The 24 h-urine total protein (24 h-UTP),serum creatinine (Scr) and blood urea nitrogen (BUN) were measured by the kit to evaluate the renal function of the mice.The pathological changes of the kidney were observed by hematoxylin-eosin (HE) and Masson staining.Real-time quantitative polymerasechain reaction (RT-qPCR) and Western blotting were used to detect the expression of EMT-related factors ［E-cadherin (E-cad),vimentin (VIM),alpha-smooth muscle actin (α-SMA),transforming growth factor beta (TGF-β)］ to evaluate the effect of CRO on EMT.The expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) related factors ［NLRP3,apoptosis-associated speck-like protein containing a CARD (ASC),cleaved-caspase-1,mature-interleukin-1 beta (mature-IL-1β),mature-IL-18］ was detected to evaluate the effect of CRO on NLRP3 pathway.The results showed that Scr,BUN,and 24 h-UTP in DKD mice treated with CRO decreased to varying degrees,and the pathological damage of renal tissue was improved to varying degrees.The expression of E-cad increased,while the expression of VIM,α-SMA,and TGF-β1 decreased.The expression of NLRP3,ASC,cleaved-caspase-1,mature-IL-1β and mature-IL-18 were down-regulated.These results suggest that CRO inhibits EMT by inhibiting NLRP3 pathway to alleviate DKD.