This work aimed to study the effect of partial replacement of monosodium glutamate (MSG) by 5΄ inosine monophosphate (5΄-IMP) on the fertility of male rats after oral administration for 90 days. Before the biological treatment, a half amount of MSG as flavor enhancer in chicken burger was replaced by 5´IMP. The sensory assessment of cocked chicken burger confirmed that this used mixture (1:1 w/w) had a synergistic effect and led to improve the flavor intensity compared to that with MSG. Treatments were applied by stomach tube (mg/kg BW); (i) MSG, [60 for adult; 30 for weaned rats]; (ii) Mixture (1:1; w/w) of MSG and 5΄-IMP [30:30 for adults; 15:15 for weaned rats] and (iii) 5΄-IMP [30 for adult; 15 for weaned rats]. Body weight gain (BWG%) and weight of some reproductive organs including testes, prostate, cauda epididymes and seminal vesicles were measured. Serum testosterone and interstitial cell-stimulating hormone (ICSH) and seminal fructose content were assayed. Spermatozoa activity and the histology of reproductive organs were also studied in adult and weaned male rat groups. Severe negative effects on most studied parameters were demonstrated in MSG-groups, where the lowest fructose content in prostate, testosterone levels and spermatozoal activities were recorded. Reduction in the weight of cauda epididymes and testes was recorded in MSG-treated weaned rats. Histologically, all studied reproductive organs were dramatically affected by MSG-treatment. Considerable enhancements in the studied parameters and normal histological profiles were obtained due to the partial replacement of MSG by 5΄-IMP. In conclusion, 5΄-IMP has a potential protective effect against MSG-hazards in reproductive organs.