Objective To observe the expression of heparanase (HPA) in kidney of diabetic nephropathy (DN) rats and to investigate the role of HPA in the pathogenesis of proteinuria in DN rats. Methods DM rat models induced by intraperitoneal injection with streptozotocin were constructed. Twenty-six rats were randomly divided into healthy control group (n=6), DM 6-week group(n=10) and DM 12-week group(n=10). Relative kidney weight（RKW）, blood glucose, BUN, Scr, 24-hour urine volume and 24-hour proteinuria quantitation were measured, and renal morphology was observed after 6 and 12 weeks. The expression of HPA was examined by immunohistochemistry and reverse transcription PCR. Results (1) Compared with the control group, RKW, blood glucose, BUN, 24-hour urine volume and 24-hour proteinuria quantitation of DM groups increased markedly(P< 0.05 or P<0.01).(2) Compared to the control group, the expression of HPA mRNA and protein in DM groups increased significantly (P<0.01). (3) HPA protein and mRNA were positively correlated with the quantification of urinary protein (r=0.783, P<0.01; r=0.793, P<0.01). Conclusion The increased expression of HPA maybe participate in the pathogenesis of proteinuria in DN.