This study investigated the anti-proteinuric effect of sulodexide in rats with adriamycin (ADR) nephropathy. A total of 40 healthy male Sprague-Dawley (SD) rats were randomly assigned to four groups: normal control group (Control-group), ADR control group (ADR-group), sulodexide treatment group (SUL-group), and losartan treatment group (LOS-group). The ADR-induced rat models were established by injecting two different doses of ADR (4 and 3.5 mg/kg) into the caudal vein of rat for two consecutive weeks. After that, SUL-group and LOS-group were respectively treated with sulodexide (10 mg/kg/day) and losartan (10 mg/kg/day) for an additional 4 weeks period. Samples of 24-hour urine were harvested at 3, 4, 5, and 6 weeks after the model establishment. The pathological change in renal tissues was observed by light microscopy, the function of liver and kidney were assayed at week 6th . The results showed that the urinary excretion of protein progressively increased in ADR-group, and accompanied with severe nephrotic syndrome such as massive albuminuria, proteinuria, and hyperlipidemia. Sulodexide effectively reduced the 24-hour urinary protein excretion of ADR-induced nephropathy rats, preventing focal segmental glomerulosclerosis. There was no significant difference between LOS-group and SULgroup for reducing urinary protein excretion (P < 0.05). Sulodexide alleviated ADR-induced nephrotoxicity as good as losartan in a short period of treatment.