This study aimed to investigate the association between HLA DR/DQ and inflammatory bowel diseases (IBD) in Tunisian patients and to determine the relationship between HLA DR/DQ alleles with the clinical disease patterns. DNA typing of human leukocyte antigen (HLA) genes was performed in 70 ulcerative colitis (UC) patients, 40 Crohn's disease (CD) patients, and 123 healthy controls (HC) using a polymerase chain reaction sequence specific primer technique. Data were analyzed using Cochran-Mantel-Haenszel test and binary logistic regression. Compared with HC, IBD patients showed an increased frequency of the homozygous DRB1*07 genotype. This positive association was maintained when UC and CD were separately compared to HC. In UC patients, DQB1*03:02 was predictive of colonic extension whereas DRB1*13 and DQB1*03:01 were associated limited disease localization (left-sided colitis and proctitis). The DRB1*15 allele increased in patients with extraintestinal manifestations. In CD, female patients showed an increased frequency of DRB1*13, DRB1*15, and DQB1*06 alleles and DRB1*13-DQB1*06 haplotype, whereas a significant increase of DRB1*07, DQB1*02 alleles, and DRB1*07-DQB1*02 haplotype was noted in male patients. These results show a significant association of the homozygous HLA-DRB1*07 genotype with UC and CD and of several HLA DR/DQ alleles and haplotypes with the clinical phenotypes of these diseases in Tunisian patients. Because of limited statistical power, our study findings are subject to further investigation.