The present study was carried out to evaluate the ability of using Pawpaw (Carica papaya) seeds powder (PSP) as natural reproductive inhibitor for Nile tilapia (Oreochromis niloticus) to control their propagation. The experiment was divided into two periods; the first was the treating period (1st) during which the Nile tilapia fry were treated with PSP for 71 days and the second was the rearing period whereas the Nile tilapia fingerlings (2nd) obtained from the first period until sexual maturation stage for 84 days. The PSP was added to the basal diet at levels of 0, 2, 4, 6 and 8 g/kg diet for 15, 30, 45 and 60 days, different periods (1st). Results of the 2nd period showed that there were no significant (P ≥ 0.05) effects on total cholesterol, testosterone and progesterone hormones among all periods; however the testosterone and progesterone hormones were decreased (P ≤ 0.01) by increasing levels of PSP. Also, the high levels of PSP (4, 6 and 8 g / kg diet) and increasing exposure periods (30, 45 and 60 day) caused obvious histological alternations of testes and ovaries of O. niloticus which reduce the fertility of both males and females. Consequently, it could be recommended that the effectiveness use of PSP as a natural reproductive inhibitor for O. niloticus.