Background: The present study aimed to assess the therapeutic effect of chitosan nanoparticles and metronidazole against Giardia lamblia as well as evaluate the efficacy of loading metronidazole on chitosan nanoparticles. Methods: This study was carried out at medical Parasitology Department, Faculty of Medicine, Zagazig University and Theodor Bilharz Research institute (TBRI) from February 2019 to February 2020 on 45 hamsters. They were divided into 5 groups 9 hamsters each: Group A non-infected hamsters, Group B infected control group, Group C, D and E infected with G. lamblia and treated with Chitosan nanoparticles (CsNPs), metronidazole (MTZ) and metronidazoleloaded chitosan nanoparticles (MTZ-CsNPs) respectively. Results: The highest percentage of reduction in the Giardia cyst and trophozoite counts were in group that received MTZ-CsNPs (94.69%, 94.29%). Lower percentages of reduction were recorded for MTZ treated group (90.15%, 89.52%) and CsNPs treated group (63.64%, 75.24%). Histopathological examination showed marked healing of intestinal mucosa after treatment with MTZCsNPs. Conclusion: CsNPs showed a therapeutic effect against Giardia infection in hamsters. Loading of metronidazole on chitosan nanoparticles enhanced therapeutic effect of both CsNPs as well as metronidazole.

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