Abstract: OBJECTIVE To observe the preventive and therapeutic effects of hydroxysafflor yellow A combined with astragaloside Ⅳ on chronic kidney disease in rats and to explore its mechanism. METHODS 36 male Sprague-Dawley rats were randomly divided into sham operation group， model group and treatment group (HSYA+As-Ⅳ) by rat 5/6 nephrectomy model. One week after continuous administration， rats were sacrificed one month later. Serum levels of serum creatinine (Scr) and urea nitrogen (BUN) were measured before and after treatment in each group. The levels of SOD and MDA were measured to show oxidative stress changes. HE staining was used to observe the small groups. Histopathological changes in rat kidney， Western blot was used to detect SIRT1， eNOS and PGC-1α protein in kidney tissues of mice. RESULTS Compared with the model group， the treatment group reduced the levels of increased SCr and BUN， improved renal pathological changes， significantly reduced renal oxidative stress， and increased the expression of SIRT1， eNOS and PGC-1α proteins. CONCLUSION HSYA combined with As-Ⅳ may exert anti-chronic kidney disease through SIRT1/eNOS/PGC-1α pathway and oxidative stress.