Radish (Raphanus sativus) has been extensively studied for its preventive effects against different degenerative diseases. Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp and is frequently implicated in immunological disorders and occasionally in hyperoestrogenic syndromes contributing to the increased risk of cancer and other diseases. The aims of this study were, firstly, to quantitatively evaluate the Tunisian radish extract (TRE) for its total flavonoids, isothiocyanates and antioxidant activity and, secondly, to investigate the protective role of TRE against immune system disorders in Balb/c mice treated with ZEN for two weeks. The results indicated that mice treated with ZEN (40 mg kg(-1)) alone showed a significant decrease in lymphocytes of the total white blood cells, immunoglobulin profile (IgG and IgM), B cells, T-cell sub-types (CD3+, CD4+ and CD8+) and natural killer and pro-inflammatory cytokines. Mice treated with TRE (5, 10 or 15 mg kg(-1)) for 7 days before, during or after ZEN treatment, however, showed a significant improvement in lymphocyte, immunoglobulin profile, T-cell sub-types, B cells and pro-inflammatory cytokines. Moreover, treatment with the highest dose of TRE (15 mgkg(-1)) enhanced the release of tumour necrosis factor-alpha and interleukin-1beta but the other parameters were comparable with those of the control. It could be concluded that TRE was effective in protecting against ZEN-induced immunological disorders. These results supported our hypothesis that TRE contains several compounds that are able to prevent or inhibit ZEN toxicity.