Background and Aims Heme oxygenase 1 is an essential enzyme in heme catabolism induced by oxidative stress.It induced in avariety of kidney substructres in response to injury, including proximal tubules, glomeruli and renal interstitium.We aimed to assess the possible role of heme Oxygenase-1 as a potential marker in early diagnosis of diabetic nephropathy. Method This case control study was conducted in Ain Shams university hospital, Cairo, Egypt. It included 80 type 2 diabetic patients diagnosed according to the American Diabetes Association (ADA) criteria, with and without DN ,and 20 healthy control subjects matched in age and sex .Patients were divided into two groups according to the value of the urinary albumin-to-creatinine ratio (ACR) : Group I: 40 normoalbuminuric patients(16 M and 24 F) with ACR<30 mg/g, and Group II: 40 microalbuminuric patients (18M and 22 F) with ACR 30-300mg/g. We excluded patients with history of diabetic ketoacidosis or hypoglycemic coma in the past 3 months preceding the study. Patients with glomerulonephritis, nephrolithiasis, tumors or any other renal diseases were excluded as well. For all studied groups,full history taking and clinical examination were done. We assessed glycosylated hemoglobin (HbA1C),blood urea, serum creatinine, urine creatinine, urinary albumin-to creatinine ratio (ACR mg/g) ,and urinary hemeoxygenase 1(UHO-1) by ELISA . Glomerular filtration rate (eGFR) was estimated by modification of diet in renal disease formula(MDRD)and uHO-1/cr was calculated. Results Group I patients were diabetic for 6.18±0.75 years, while group II patients for 6.05±0.81 years(p = 0.477). Normoalbuminuric patients had significantly higher levels of uHO-1 compared to control (3.01ng/ml vs 0.3 ng/ml,p<0.001).UHO-1 reached highest value among the microalbuminuric group (5.02 ng/ml) with P<0.001.UHO-1/cr ratio was significantly positively correlated with urinary ACR (r = 0.61,p<0.001) and significantly negatively correlated with eGFR(r = -0.71,p <0.001). There was highly significant correlation between uHO-1and eGFR by linear regression. ROC curves showed that AUC of uHO-1is comparable to uHO-1/ Cr ratio (0.957 vs 0.954) respectively with equivocal sensitivity 100 % and specificity 95% and cut off value of uHO-1 >0.46 ng/mland > 0.7 for uHO-1/ Cr ratio. Conclusion UHO-1 is increased in normoalbuminuric patients before the presence of any proteinuria and level increased with the progression of proteinuria and falling of eGFR as well as with the uncontrol of diabetes. UHO-1 is more sensitive than albumin for the detection of early diabetic nephropathy.