Eimeria stiedae is the most pathogenic rabbit Coccidia. This study was designed to clarify hematological, biochemical, and pathological alterations associated with hepatic coccidiosis in rabbits and to investigate the effect of diclazuril on the course of the disease for both protection and treatment. Rabbits experimentally infected with 2×10⁴ sporulated oocysts of E. stiedae. Rabbits were equally divided into 4 groups. Group 1, non-infected non-treated, was served as control negative. Group 2 was considered a control positive. Group 3 treated on the day 10 post-infection with a dose of 5 ppm of diclazuril given orally in drinking water for 2 days. Finally, group 4 or the protected group was administered diclazuril at a dose of 1 ppm orally in drinking water for seven days before infection. Blood and serum samples were collected at 18^th, 25^th, 32^th, and 39^th days post-infection. Rabbits of group 2 showed significant alterations of hematological parameters [reduced of RBCs, Hb, MCV, lymphocyte counts and increased of TLC, Neutrophil counts]; serum biochemical parameters [reduced concentrations of total protein, albumin, calcium, and increase of bilirubin, urea, enzymatic activities of ALT, AST, ALP, GGT]; and histological picture of liver indicated hepatic coccidiosis, while rabbits either treated by or protected with diclazuril showed no significant hematological, biochemical and histopathological changes from negative control. In conclusion, diclazuril appeared to be a potent anticoccidial drug against E. stiedae infection in rabbit either for treatment or as prophylaxis.