Rheumatoid arthritis is the most common systemic, autoimmune rheumatological disorder. The purpose of this study was to determine the relationship between IL-1β -511 promoter and IL-1β +3953 exon 5 genes' polymorphisms and susceptibility to Rheumatoid arthritis and disease activity in Egyptian patients. Genotypes of IL-1β -511 promoter and IL-1β +3953 exon 5 genes were detected by polymerase chain reaction followed restriction fragment length polymorphism. No special pattern of association could be detected either between IL-1β -511 and +3953 gene polymorphisms and disease susceptibility or between the polymorphisms and the disease activity parameters represented by DAS 28, ESR and number of swollen and tender joints. Allele distribution failed as well to detect any association with either disease susceptibility or activity, however a trend towards positive association involving IL-1β -511 C allele was observed. These results imply that the two genes' polymorphisms do not play a role in either rheumatoid arthritis susceptibility or disease activity.