Abstract: Objective To investigate the regulatory mechanism of breviscapine to neuropeptide Y(NPY) and itsY₂re-ceptor(Y₂R) in diabetic nephropathy.Methods The maleW istar rats were randomly allocated to three groups:normal control,strep to zotoc in-induced diabetes,and diabete streated with breviscapine group.After 28 days,the rats were sacrificed.Thelevel of NPY in plasm a and renal cortex,the urine a lbumin excretion ratio(UAER) were measured with radiomimuno assay(RIA).RT-PCR,immunoh isto chemistry(IHC),and computer software for image analysis were used to evaluate the expression of NPY mRNA and Y₂R.Blood glucose,body weight,kidney weight,and Na⁺,K⁺-ATPase activity were measured.Results Compared with diabetes mellitus group,the blood glucose(20.02±2.89 mmol/L)and UAER(1.03±0.19 μg/min) of diabetic rats were ameliorated by breviscapine treatment.Compared with diabete smellitus group,the plasma and renal cortical NPY concentrations(4.453±0.245 ng/mL and 0.66±0.08 ng/mg)and Na⁺,K⁺-ATPase activity(3.29±0.80 μmol Pi/mg protein/hr) were significantly decreased in breviscapine treatment group(P < 0.05).The expres-sions of NPYmRN A and Y₂R protein were significantly decreased to 30.2% and 26.3% in the renal cortex of diabetic ratstreated with breviscapine compared with that of diabetic rats(P < 0.05 for both).Conclusion Breviscapine can down-regu-late expressions of NPY mRNA and Y₂R,then inhibit Na⁺,K⁺-ATPase activity in renal cortex and there fore improve thedamage in diabetic nephropathy.