Abstract: Objective To investigate the protective effects and mechanisms of Tanshinone ⅡA (Tan ⅡA) on diabetic kidney disease (DKD) in rats.Methods A rat model of DKD was established using a high-fat diet combined with streptozocin (STZ) injections. The experimental animals were divided into control group, model group, Tan ⅡA group, and valsartan group. During the experiment, the alterations in body weight and blood glucose levels of each cohort of rats were continuously monitored, blood and urine samples were collected for biochemical markers analysis. Kidney tissues were collected for Hematoxylin-Eosin (HE) staining, Periodic Acid Schiff (PAS), transmission electron microscopy, and immunohistochemical detection.Results Tan ⅡA was found to increase the body weight of DKD rats (P<0.01), decrease the blood urea nitrogen (BUN), 24-hour urinary protein, and serum creatinine (Scr) levels (P<0.05), with no significant differences in fasting blood glucose (FBG) among the drug groups. Moreover, the renal tubular injury score after HE staining and the count of PAS-positive mesangial areas in glomeruli in Tan ⅡA group were both reduced compared to the DKD group (P<0.05). Tan ⅡA effectively improved oxidative stress and pyroptosis in rats with DKD. Transmission electron microscopy showed that the cell membrane damage in glomerular microvascular endothelial cells (RGMEC) of the Tan ⅡA and valsartan groups was significantly reduced. The expression of Txnip and Nlrp3 were significantly decreased in the Tan ⅡA and valsartan group (P<0.01).Conclusions Tan ⅡA has been observed to potentially delay the progression of DKD by inhibiting glomerular microvascular endothelial cell pyroptosis in rats through regulating Txnip/Nlrp3 inflammasome.