Monosodium glutamate (MSG) has been identified as a food additive that Adversely affects MSG use on the reproductive efficiency by several mechanisms, this study was carried out to determine its role in stimulating the immune response in the reproductive system by estimating levels of NF-κB in serum and of its expression in reproductive organs. Thirty sex males rats were used in this study each included 12 male rats. Male rats A and B are receiving 60 and 120 mg/kg for 28 days respectively male rats of the control group were left without treatment for the period of the experiment. The levels of Nuclear factor-kappa NF-κB in serum and tissue fluid of testes and epididymis were measured. histological changes in addition to detection NF-κB expression were studying in testes and epididymis. Results of the present study recorded the toxic effect of MSG as it caused an elevation in the levels of NF-κB in serum, testicular, and epididymis tissue fluid. histological alternation in the reproductive organs was observed to represent detachment and vacuolation of the seminal epithelium, degeneration of spermatogenesis edema in a lumen in testicular tissues. Epididymal sections appeared to sever necrosis, degeneration in the epithelial layer and stereocilia, and the lumen of the epididymis. Also there was an increasing density of NFκB protein immunoreactivity in both testis and epididymis.