Aim: This study investigated the suppressive effect of saponin from Vitex doniana leaf on Ki-67 immunomarker and prostate specific antigen in prostate toxicity induced with Nitrosobis (2-oxopropyl) amine. Material and Method: The male Wistar rats used for this experiment were grouped into 5 groups of 4 rats each. The experiment lasted for 28 days. From day 1-14, group 1 received subcutaneous normal saline 0.5ml daily, while groups 2, 3, 4, and 5 received Subutaneous Nitrosobis (2-oxopropyl) amine 5mg/kg daily. From day 15-28, group 1 received oral normal saline 0.5ml daily, while groups 3, 4, and 5 received oral saponin at 250mg/kg, 500mg/kg, and 750mg/kg daily, respectively. Group 2 did not receive nitrosobis (2-oxopropyl) amine nor saponin from day 15-28. All the rats had free access to commercial rat chow throughout the experiment. Results: Significant increase (p<.05) in prostate Ki 67 immunomarker expression and serum prostate specific antigen level were observed in group 2 (Nitrsobis amine only) when compared with group 1 (normal saline). There was decrease in the level of expression of Ki-67 immunomarker in group 3 (Nitrosobis amine plus Saponin 250mg/kg), and group 4 (Nitrosobis amine plus Saponin 500mg/kg when compared with group 2. However, this decrease was not statistically significant (p>.05). There was statistical significant decrease (p<.05) in Ki-67 expression in group 5 (Nitrosobis amine plus Saponin 750mg/kg) when Compared to group 2. Significant decrease in the level of serum prostate specific antigen was observed in groups 4, and 5, when compared to group 2. There was no significant decrease in prostate specific antigen level in group 3 when compared to group 2. Conclusion: Saponin fraction of Vitex doniana significantly reduced the prostate Ki-67 immunomarker expression and serum prostate specific antigen concentration in the dose studied. Thus saponin may be an agent that could be employed to reduce disease arising from prostate toxicities, such as prostate cancer.