The aim of the study is to evaluate the combined effect of Mast cell stabilizers and varicocelectomy on DNA fragmentation index using Halosperm kit®. Patients and methods: This study was carried out on sixty patients with abnormal seminal bulk parameters and grade II or III varicocele, complaining of primary infertility of more than one year duration. Patients were divided into three groups: Group (1) Twenty patients who had varicocele repair, Group (2) Twenty patients who received only Mast cell stabilizers for 3 months and Group (3) Twenty patients who had combined varicocele repair and Mast cell stabilizers for 3 months after surgery. Results: There was an improvement in DNA fragmentation in each group after treatment Group (1) (P value 0.032), Group (2) (P value 0.021), Group (3) (P value 0.000) however there was no statistically significant difference when comparing the three groups with each other concerning the improvement in the DNA fragmentation index. Conclusion: Mast cell stabilizers and varicocelectomy improve DNA fragmentation, combined treatment can be offered to patients with elevated level of DNA fragmentation above 30% causing repeated ICSE failures, we also recommend continuing the research on a larger scale and on an extended period of follow up.