Abstract: Objective: To observe the expression of midkine and HGF in the renal tubles of diabetic rats and to investigate their relationships .Methods:sixty male Sprague-Dawlry rats were randomly divided into two groups:normal control group(n=24)and diabetes mellitus group(n=36).Type 2 diabetic nephropathy were induced by high-glucose and high-fat diet and intraperitonesl STZ after unilateral nephritic excision. At the end of 6th week and the 12th week after diabetes mellitus model established,blood glucose and 24 hours urine protein were determined,and body weight were weighed,and then rats were killed to collect the serum and kidney.We calculated the ratio of kidney weigh to body weigh(KW/BW). The tubular structural changes were examined with HE staining and periodic acid-silver methenamine staining at 6th week and the 12th week. The protein expression of midkine and HGF intubular-interstitial were determined by immunohistochemistry.Results:(1) FBG,KW/BW and 24 hours urine protein were obviously increased in the diabetes mellitus group compared with normal control group(P<0.05).(2) There were severe structural alterations of tubular-interstitium in diabetes mellitus group .(3) At the end of the 6th week, the12th week after diabetes mellitus model established,immunohistochemistry revealed a significant increase in the expression of MK and HGF in the kidney in diabetes mellitus group compared with normal control group(P<0.01). At the end of the 12th week , the expression of MK was obviously increased In diabetes mellitus group compared with the 6th week(P<0.05), the expression of HGF was obviously decreased In diabetes mellitus group compared with the 6th week(P<0.05).(4) In diabetes mellitus group,there were negative correlations between midkine and HGF(r=-0.525,P<0.01).Conclusion: The expression of midkine and HGF in tubular-interstitium are unbalanced,which possibly participated in pathogenesis of diabetic nephropathy.

Key words: type 2 diabetic nephropathy, tubular-interstitial, Midkine, hepatocyte growth factor