Background: Increased intestinal permeability, either due to the exposure to antigens in asthmatic patients or due to a barrier defect, play a critical role in susceptibility to environmental allergens. House dust mites allergy occurs more commonly than any other allergens among Egyptian asthmatic patients. Aim: To assess the relation between serum zonulin level as a marker of increased intestinal permeability and the severity of house dust mites allergic asthma. Methods: A case control study which included 96 subjects attending the allergy and immunology unit, microbiology and immunology department, Faculty of medicine, Zagazig University. They were divided into 48 house dust mites allergic asthma and 48 healthy control subjects. Results: On comparing the 2 studied groups, there was a statistically significant difference between the 2 groups concerning serum IgE and serum zonulin levels ( p=0.000, 0.000 respectively)The mean serum zonulin was equal to 258.3±153.01 ng/ml in the asthmatic group and 80±13 ng/ml in the control group. Serum zonulin level significantly increased with the increase of asthma severity (p˂0.001). The cut off value of serum zonulin was ≥ 198 ng/ml, and the area under the curve was 0.76. It displayed sensitivity equal to 80% and specificity equal to 71.4%. Its negative predictive value was equal to 83.3%. Conclusion: Intestinal barrier dysfunction contributes in the pathogenesis of allergic asthma. Serum zonulin level reflects an increase in intestinal permeability and acts as prognostic factor of severity in Asthma. Correction of the gut barrier defect may be an additional novel approach for Asthma.