To study the effects of high-sucrose and high-fat diet on tubulointerstitial fibrosis,male New Zealand white rabbits(Oryctolagus cuniculus) were randomly divided into two groups:the control group(n=10,fed with normal chow) and the experimental model group(n=10,fed with 37% sugar,10% lard and 53% normal chow).The levels of fasting plasma glucose and triglyceride were tested once a month.Urinary glucose,microalbumin,and N-acetyl-β-glucosaminidase(NAG) were measured at the end of the 5th month.The tubulointerstitial fibrosis index(TIFI) and the area of collagen fiber were calculated in the renal medulla with HE or VG staining respectively.The protein expression of type Ⅳ collagen,fibronectin and transforming growth factor β1(TGF-β1) were determined by immunohistochemical staining.Feeding high-sucrose and high-fat diet to rabbits markedly caused hyperglycaemia,hypertriglyceridemia,albuminuria,glucosuria,and increased urinary NAG levels(P<0.05 or P<0.01).The edema,inflammatory cell infiltration and proliferation of collagen fiber were observed in tubulointerstitium of the experimental model group.The area of collagen fiber 22.47%±5.66% and the grade of TIFI 2.369±0.6734 were significantly higher in the experimental model group than those in the control group(9.43%±3.03% and 0.6810±0.2248,P<0.01,respectively).The protein expression of type Ⅳ collagen,fibronectin and TGF-β1 was significantly increased in renal medulla of the experimental model group compared to that of the control group(P<0.01).Thus,these results suggest that high-sucrose and high-fat diet can injure the tubulointerstitial structure and function,increase the expression of extracellular matrix and accelerate the process of tubulointerstitial fibrosis in rabbits.