Inclusion Criteria:

• Diagnosis of type 2 diabetes;
• Urine protein to creatinine ratio (PCR) equal to or greater than 900 mg/G (101.7 mg/mmol) in women and equal to or greater than 650 mg/G (73.45 mg/mmol) in men;
• Serum creatinine in women 1.3 - 3.0 mg/dL (115-265 μmol/L), inclusive, and in men 1.5 - 3.0 mg/dL (133-265 μmol/L), inclusive;
• Willing to discontinue antihypertensive medication regimen, if applicable;
• Willing and able to give informed consent.

Exclusion Criteria:

• Type 1 (insulin-dependent; juvenile onset) diabetes;

• Renal disease as follows:

  • Patients with known non-diabetic renal disease (nephrosclerosis superimposed on diabetic nephropathy acceptable), or
  • Renal allograft;
• Absolute requirement for combination therapy of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB);
• Patients who require ACEI, but not ACEI/ARB combination;

• Cardiovascular disease as follows:

  • Unstable angina pectoris within 3 months of study entry;
  • Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 months of study entry;
  • Transient ischemic attack within 3 months of study entry;
  • Cerebrovascular accident within 3 months of study entry;
  • New York Heart Association Functional Class III or IV (Note: if a patient is New York Heart Association Functional Class I or II and requires an ACEI, consult with the Clinical Coordinating Center to obtain permission for the patient to be on an ACEI rather than an ARB);
  • Obstructive valvular heart disease or hypertrophic cardiomyopathy; or
  • Second or third degree atrioventricular block not successfully treated with a pacemaker;
• Need for chronic (>2 weeks) immunosuppressive therapy, including corticosteroids (excluding inhaled or nasal steroids);
• New diagnosis of cancer or recurrent cancer within 5 years of screening (except non-melanoma skin cancer);
• Psychiatric disorder that interferes with the patient's ability to comply with the protocol;
• Inability to tolerate oral medication or a history of significant malabsorption;
• History of alcohol or other drug abuse within 12 months of study entry;
• Known human immunodeficiency virus disease;
• Any other medical condition which renders the patient unable to or unlikely to complete the study, or which would interfere with optimal participation in the study or produce significant risk to the patient;
• Receipt of any investigational drugs (including placebo) within 30 days of enrollment;
• Evidence of hepatic dysfunction including total bilirubin >2.0 mg/dL (>35 micromol/L) or liver transaminase (aspartate aminotransferase [AST] or alanine transferase [ALT]) >3 times upper limit of normal;
• Anticipate need for surgery;
• Inability to cooperate with study personnel or history of noncompliance to medical regimen;
• Known allergies or intolerance to any heparin-like compound including heparin-induced thrombocytopenia Type II;
• Prior exposure to sulodexide, either in a clinical setting or as a participant in another clinical study.
• Untreated urinary tract infection that would impact urinary protein values.