To explore the protective effect of echinacoside on acute kidney injury (AKI) in septic rats, and explore the possible mechanism. Methods Fifty-five SD rats were taken, 10 were randomly selected as the control group, and the remaining rats were established as a sepsis model. Forty animals were successfully divided into model group, echinacoside low-dose group, echinacoside medium-dose group, and echinacoside high-dose group, with 10 animals in each group. Echinacoside (25, 50, 100 mg/kg) was injected into the tail vein in the low, medium and high dose groups of echinacoside, and the control group and model group were injected with the same amount of DMSO. They were given once at 6, 12, and 18 h after operation. Flow cytometry was used to detect the ratio of Th1 and Th2 in peripheral blood. Serum inflammatory factors were tested. Serum renal function indicators were tested. HE staining was used to observe the histopathological changes of renal tissue. Western blotting was used to detect the expression of renal interleukin-13 (IL-13), Janus protein tyrosine kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription 3 (STAT3), and p-STAT3 protein expression. Results Compared with the model group, the peripheral blood Th2 composition ratio, serum IL-6, IL-8, urea nitrogen (BUN), serum creatinine (Scr) level, Kidney tissue IL-33 protein expression, p-JAK2/JAK2, p-STAT3/STAT3 in the echinacoside low, medium and high dose groups were decreased, and Th1 composition ratio, Th1/Th2 were increased (P＜0.05). Compared with the echinacoside low dose group, the peripheral blood Th2 composition ratio, serum IL-6, IL-8, urea nitrogen (BUN), serum creatinine (Scr) level, Kidney tissue IL-33 protein expression, p-JAK2/JAK2, p-STAT3/STAT3 in the echinacoside medium dose group were decreased, and Th1 composition ratio, Th1/Th2 were increased (P＜0.05). Compared with the echinacoside medium dose group, the peripheral blood Th2 composition ratio, serum IL-6, IL-8, urea nitrogen (BUN), serum creatinine (Scr) level, Kidney tissue IL-33 protein expression, p-JAK2/JAK2, p-STAT3/STAT3 in the echinacoside high dose group were decreased, and Th1 composition ratio, Th1/Th2 were increased (P＜0.05). HE staining results showed that the renal tissue structure of the control group was intact and the shape was normal; the renal tissue structure of the model group was severely damaged, the glomerular matrix increased, the mesangial area was thickened, and a large number of inflammatory cells were infiltrated; The thickening of the mesangium and the infiltration of inflammatory cells were reduced in the high-dose group, and the improvement was more obvious in the middle and high-dose groups. Conclusion Echinacoside can repair the homeostasis of the immune system, inhibit inflammation, and protect renal function. It is speculated that its mechanism may be related to the inhibition of IL-33/STAT axis activity