Abstract: Background: In the present study, aqueous extract of dried papaya seeds (Carica papaya Linn.) (AEP) tended to have trematodes anthelmintic activity on encysted metacercariae (EMC) and adult flukes according to the method of preparation of AEP and the concentration of the active principles. Materials and Methods: Prohemistomatidae EMC were isolated from muscles of Clarias gariepinus and divided into three groups, two of them were in vitro treated with AEP, boiled (BAEP) and soaked (SAEP) then used for experimental infection of mice. The 3rd group of EMC (without treatment) were used for experimental infection of mice which then were in vivo treated with BAEP and SAEP after development of adult flukes. Scanning Electron Microscopy (SEM) was performed to study the ultrastructure changes of the tegument surface of adult Prohemistomum vivax treated with AEP. Results: Carica papaya, aqueous seed extracts resulted in a significant reduction of total count of egg output and morphological changes. Scanning electron microscopy revealed P. vivax showed edema and wrinkle on the body surface. Deformities of the anterior and middle spines, bending at the border of the spines, blistering and rupturing at the body surface were noticed in the worms. Conclusion: The present study confirmed the promising anthelmintic property of the C. papaya seed aqueous extract where it create tegumental surface changes of Prohemistomum vivax flukes demonstrated by Scanning Electron Microscope (SEM). The boiled aqueous extracts of C. papaya seeds have strong anthelmintic activity that encourages its future application in aquaculture.