This study was conducted to evaluate the histological changes of 17αmethyl-testosterone (MT), wet testes of bull (Bos indicus), boar (Sus domesticus), bull/mud catfish testes (B. indicus/C. gariepinus) and pawpaw (Carica papaya) seed powder-based diet on the Nile tilapia fry in an indoor experimental pond. Histological changes and efficacies in producing monosex males were determined after four months. Fifty-five fry were assigned randomly to three experimental ponds in triplicates. Five experimental feeds composed of soya-bean, fish meal, wheat bran, cassava flour were formulated by adding 0.06g of 17α- methyl-testosterone, 17.47g of bull wet testes, 25.59g of boar wet testes, 20.48g of bull/catfish and 20g of pawpaw seed powder per kg of feed to group 1, 2, 3, 4, 5 respectively. Obtained results from the morphological examination revealed a significant difference (p < 0.05) in phenotypic males of the Nile tilapia fry fed with the experimental diets. The highest indistinct percentage was recorded in the 17αmethyl-testosterone-treated diet while the lowest was recorded in diets 3 and 4 with no significant differences. All the groups showed histopathological differences in the livers, gills, and muscles. However, the liver histology of groups 1 and 5 showed central vessels that are mildly congested with abundant glycogen vacuolation and somewhat fat infiltration, while the histology of the muscles of group 5 showed pathological lesions including moderate to severe necrosis. These alterations can be considered an indication of the performance and health of fish in monosex culture medium indicating effects of plant extract and MT.