The present study was conducted to evaluate the efficacy of oral administration of fenbendazole (20 mg/kg body weight) prior and after experimental infection of immunosuppressed rabbits with Encephalitozoon cuniculi. A total of thirty rabbits were divided into five groups; NN (non-immunosuppressed; non-infected); IN (immunosuppressed noninfected); IPI (immunosuppressed prophylactic-infected); ITI (immunosuppressed treatedinfected) and II (immunosuppressed infected) groups. Fenbendazole was administered as a prophylactic for seven successive days before infection with E. cuniculi and as a treatment for four weeks initiated on the 28th day post-challenge (PC). Experimental rabbits were infected with intraperitoneal injection of 2x105 E. cuniculi spores. Parameters evaluated were body weight, detection of spores in urine, serum antibody assay, hematological, biochemical and histopathological changes. The IPI and ITI groups showed a significant better final bwt than the II group. Spores were detected in the urine of all infected rabbits from the 28th day PC and until the end of the study. The IPI group showed the least values of antibodies (IgG) compared to the ITI and II groups. Concerning histopathological changes, the intensity of the lesions was marked particularly in the II rabbits and to a lesser extent in the ITI rabbits, while, a noticeable improvement was found in the IPI rabbits. It could be concluded that fenbendazole was effective to some extent as a prophylaxis for rabbits against E. cuniculi infection, while when administered as a therapeutic did not display significant effects.