OBJECTIVE To evaluate the effect of zinc supplementation on immunotoxicity induced by subchronic oral exposure to glyphosate-based herbicide (GBH). METHODS Sixty adult male Wistar rats randomly divided equally into six groups were exposed to GBH by gavage daily for 16 weeks with or without zinc pretreatment. Group DW rats received distilled water (2 mL/kg), group Z rats received zinc (50 mg/kg), and group G1 and G2 rats received 187.5 and 375 mg/kg GBH, respectively. Group ZG1 and ZG2 rats were pretreated with 50 mg/kg zinc before exposure to 187.5 and 375 mg/kg GBH, respectively. Tumor necrosis factor alpha (TNF-α) and immunoglobulin (IgG, IgM, IgE) levels were measured by enzyme-linked immunosorbent assay. Spleen, submandibular lymph node, and thymus samples were processed for histopathology. RESULTS Exposure to GBH (G1 and G2) significantly increased serum TNF-α concentrations and significantly decreased serum IgG and IgM concentrations compared with the control levels. Moderate-to-severe lymphocyte depletion occurred in the spleen, lymph nodes, and thymus in the GBH-exposed groups. Zinc supplementation mitigated the immunotoxic effects of GBH exposure. CONCLUSIONS GBH exposure increased pro-inflammatory cytokine responses, decreased immunoglobulin production, and depleted lymphocytes in lymphoid organs in rats, but zinc supplementation mitigated this immunotoxicity.