Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. This study was aimed to investigate the relationship between the rs27044 polymorphism in Endoplasmic reticulum aminopeptidase-1 (ERAP-1) with the susceptibility and severity of AS correlated with some biochemical markers such as hematological parameter (Erythrocytes sedimentation rate (ESR)) and immunological parameters (C-reactive protein (CRP), Human leukocyte antigen-B27 (HLA-B27), Interlukin-6 (IL-6) and Interlukin-23 (IL-23)), and oxidative stress parameters (Glutathione (GSH) and Malondialdehyde (MDA)) in a sample of Iraqi population. A total of 60 blood samples were collected from AS patients requited Rheumatology Consultation Clinic in Baghdad Teaching Hospital in Baghdad Governorate. Those patients are males and females with age ranged between 26- 32 years for early diagnosed patients (10 samples) and other medically treated patients with age ranged between 22-52 years (50 samples). The rest (30 blood samples) were collected from healthy controls with age ranged between 16-68 years. Results showed that there is a significant increase in Erythrocytes Sedimentation Rate (ESR) as a hematological parameter in newly diagnosed and medically treated patients. For the immunological parameters, results showed that C-reactive protein (CRP) was detected in all serum samples taken from newly diagnosed patients, and 80% positive were detected in medically treated patients in comparison with 100% negative results in healthy controls. On the other hand, Human leukocyte antigen-B27 (HLA-B27) was also detected in all serum samples taken from newly diagnosed patients and 76% positive were recorded in medically treated patients as compared with negatively resulted in healthy controls. For the Interleukins (IL-6 and IL-23), results showed that there is a significant increase in levels of both interleukins in serum samples of newly diagnosed patients compared with healthy controls and medically treated patients, in which any significant difference was recorded. Results of oxidative stress parameters showed that there is a significant decrease in Glutathione (GSH) levels in serum samples of newly diagnosed patients compared with its level in serum sample of controls and medically treated patients, in which significantly not different. Results also showed that there is a significant increase in Malondialdehyde (MDA) levels in serum samples of newly diagnosed patients compared with its levels in healthy controls and medically treated patients, in which no significant difference in MDA levels in serum samples of both groups. Genetic polymorphism of ERAP-1 gene (rs27044 SNP) in exon15 within chromosome 5 was studied. The genomic DNA was extracted from blood samples for controls and AS patients at concentrations of extracted DNA was ranged between 100-200 ng/μl with purity of 1.8-2.0. Exon 15 was amplified by using specific primers results showed that a single band of 298 bp was obtained after electrophoresis on agarose gel (2%) represents the complete nucleotide sequence of exon 15. Results showed that the single nucleotide polymorphism (rs27044) was cSNP in all controls, while gSNP was found in 64% of polymorphic AS patients with a significant difference than non-polymorphic AS patients (36%).