BACKGROUND: Diabetic retinopathy (DR) is the most frequent microvascular complication of type I diabetes (T1D). Some well-controlled type I diabetics may develop DR, while other poorly-controlled diabetics do not develop DR. This might be explained by certain susceptibility genes or protective genes. The purpose of our study is to search for any association between the HLA class I and II markers and DR in the Algerian population. PATIENTS AND METHODS: This study was carried out in 52 T1D subjects with and without DR compared to 140 healthy controls. HLA typing was performed using the "microlymphocytotoxicity" technique. RESULTS: The frequency of HLA-A29 and HLA-DR9 antigens is higher in T1D with DR compared to T1D without DR and to controls with frequencies of HLA-A29 (59.26% vs. 0%, OR=infinity, pc=4.6x10(-7)), (59.26% vs. 5.66%, OR=24.24, pc=7.6x10-10) and HLA-DR9 (29.63% vs. 0%, OR=infinity, pc=1.310(-3)), (29.63% vs. 4.29%, OR=9.40, pc=7.010(-5)) respectively. However, the frequency of HLA-B49 antigen is significantly lower in T1D with DR than in T1D without DR (3.7% vs. 28%, OR=0.10, pc=8.8x10(-3)) and compared to controls (3.7% vs. 22.64%, OR=0.13, pc=0.011). CONCLUSION: HLA-A29 and HLA-DR9 antigens are probably markers of susceptibility for DR while HLA-B49 antigen is probably associated with a protective effect in the Algerian population.