Abstract: Cryptosporidiosis is one of the major causes of diarrhea in immunocompetent and immunocompromised patients. It is self-limited in immunocompetent individuals. However, in the immunocompromised it can cause life threatening diarrhea and results in chronic malabsorption of fluids, vitamins and electrolytes resulting in wasting. Our study is concerned with assessing and comparing the efficacy of nitazoxanide (NTZ) alone and NTZ loaded chitosan nanoparticles (NTZ loaded CS NPs) in the treatment of experimental cryptosporidiosis using parasitological and histopathological parameters. One hundred mice were divided into 5 groups (20 mice each). Each group was divided into 2 subgroups according to the immune status [a-immunocompetent, b immunosuppressed]. group 1: control (healthy), group 2: control infected by Cryptosporidium oocysts, group 3: infected treated by NTZ, group 4: infected then treated by NTZ loaded CS NPs and group 5: infected then treated by chitosan nanoparticles (CS NPs) alone. Treatment of Cryptosporidium infected mice with NTZ loaded on CS NPs resulted in the highest significant reduction in oocysts shedding in both immunocompetent and immunosuppressed groups followed by treatment with NTZ form then by treatment with CS NPs alone. The treatment with NTZ loaded CS NPs displayed a remarkable improvement of the histopathological changes of the intestine, liver and lung while NTZ treated group showed some improvement. Treatment with NTZ loaded CS NPs in murine cryptosporidiosis gave the best results as it caused marked reduction in fecal oocysts counts and improvement of histopathological changes in immunocompetent and immunosuppressed groups.