Objective: The present study was carried out to estimate the possible role of Interleukin-4 (IL-4)RαQ576R genes polymorphism in the development of immune reaction against penicillin, as well as to study the effect of IL-4 cytokine in regulating allergic reactions.Materials and Methods: Measurement of serum IL-4 concentration was done using enzyme-linked immunosorbent assay technique; IL-4RαQ576R gene polymorphisms were genotyped using polymerase chain reaction-restriction fragment lengths polymorphisms. Comparisons for statistical significance were performed using Mann–Whitney U-test.Results: Comparing with control subjects, there was a significantly increased level of IL-4 (348.53 pg/ml) in penicillin allergic patients versus (284.72 pg/ml) in sera of control subjects. The IL-4RαQ576R alleles were significantly higher in the penicillin allergic individual compared with apparently healthy control subjects.Conclusions: Data study suggested that IL-4 cytokine have some important roles in penicillin hypersensitivity reaction, additionally the IL- 4RαQ576Rgene polymorphisms might involve in modulating of penicillin hypersensitivity.