Scavenger receptor A (SR-A) is the main receptor through which oxidized LDL (oxLDL) and advanced glycation end products get into the cells. The aim of the present study was to investigate the effect of an ACE inhibitor, perindopril, on the expression of SR-A in renal tubulointerstitium of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection with streptozotocin. The rats were then randomly divided into 3 groups: normal control group; untreated diabetes mellitus group; and diabetes mellitus group treated with the ACE inhibitor, perindopril. After a 24-week treatment, tubulointerstitial injury index was assessed on Masson's trichrome sections. The number of macrophages and the expression of SR-A protein in renal tubulointerstitium were detected by immunohistochemistry and the expression of SR-A mRNA was detected by RT-PCR. The tubulointerstitial injury index, the number of macrophages and the expression of SR-A mRNA were significantly higher in the diabetes group than the normal control group. Perindopril treatment not only attenuated the tubulointerstitial injury and the macrophages infiltration but also reduced the overexpression of SR-A mRNA in diabetic rats. The expression of SR-A protein was most obvious in renal tubulointerstitium in diabetic rats, which was attenuated by perindopril treatment. The findings of the present study indicate that perindopril may have renoprotective effects of diabetic nephropathy via inhibiting the expression of SR-A in renal tubulointerstitium.