Background: juvenile idiopathic arthritis (JIA) is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age affecting one or more joints, lasting for at least 6 weeks. PADI4 is one member of PADI gene family. The PADI gene region is located at chromosome 1p36. It codes for enzymes responsible for the posttranslational conversion of arginine residues into citrulline. There are likely to be different genetic risk factors for JIA in different ethnic groups. Therefore, here we sought an influence of HLA-SE and PADI4 on JIA susceptibility in Japanese, because both HLA-SE and PADI4 were reported as significant genetic risk factors for RA independent of ethnicity. Recently, association of PADI4 gene polymorphisms with ACPA positivity and disease activity in polyarticular JIA. Aim of the Work: the aim of this work is to investigate PADI polymorphism rs2240340 to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents and whether this single nucleotide polymorphism (SNP) is correlated with clinical parameters in JIA. Patients and Methods: the ethical approval was obtained from the hospital ethical research committee and each patient entering the study will sign an informed consent. Thirty patients included in this study with polyarticular types of juvenile idiopathic arthritis and all of them fulfilled ILAR classification criteria (2004). All were under the age of sixteen at time of diagnosis. They were recruited from Physical Medicine, Rheumatology and Rehabilitation Department at Al-Hussein and Sayed Galal University Hospitals during the period from January 2018 to June 2018.  In this study we measure PADI4 polymorphism and correlate with disease activity in polyarticular JIA in Egyptian patients. Results: association of PADI4 gene polymorphisms with ACPA positivity and disease activity in polyarticular JIA and PADI4 gene polymorphism can be used as a marker of susceptibility to polyarticular JIA. Conclusion: PADI4 gene polymorphism became a marker of susceptibility to polyarticular JIA and gene polymorphism correlated with disease activity in ACPA positivity in polyarticular positive JIA.