Roundup is a widely used herbicide because of its broad spectrum and high water solubility. It is a glyphosate-based organophosphate containing mixture of surfactants. Interference of such herbicide with immune system function can induce immune suppression and decrease of disease resistance. The objective of this study is to evaluate the effect of this herbicide on the rats immune system and to assess the potential role of Royal jelly as an immune protective in Roundup-exposed rats. Eighty male albino rats were randomly divided into four equal groups. Animals of groups I and II were given one daily dose of Roundup (1500 mg/kg BW) for four weeks. Royal jelly (300 mg/kg BW once daily) was added during the last seven days of Roundup administration in group II. Group III animals received royal jelly (300 mg/kg BW) once daily, for seven days. Animals of group IV served as a control group. All animals were given the daily doses by gastric gavage. At the end of the treatment period, all rats were subjected to biochemical analysis for serum IL-4 and INFγ levels. The results of this study revealed significant reduction of serum IL-4 and INFγ levels in Roundup-treated animals. Royal jelly administration during the last seven days of Roundup treatment has improved IL-4 levels, but this improvement wasn't statistically significant. However, it has significantly improved INFγ levels compared to Roundup-treated animals. This study signifies the immune depressant effect of Roundup. Furthermore, it refers to the role of Royal jelly administration as a protective agent against such immune suppression.