Aim: To evaluate the effect of aqueous Carica papaya seed extract on microenvironment of cauda epididymis.Methods: Adult male albino rats were intrauscularly administered with 0 (control) or 0.5 mg papaya seed ex tract/kg body weight for 7 days. Cauda epididymal tubular content was collected by micropuncture technique; epididy real luminal fluid and sperm pellets were separately analyzed. Results: The results revealed that the extract treat ment caused significant reduction, as compared with control, in total protein and sialic acid contents in both epididymal fluid and sperm pellet. As compared with control, significantly lowered acid phosphatase activity was recorded in spermpellet but was higher in epididymal fluid after the treatment. The extract treatment also caused significant reduction in level of inorganic phosphorus in the ePididymal fluid. Conclusion: It is concluded that the aqueous papaya seed ex tract alters cauda epididymal microenvironment.