Giardiasis is a protozoal infection of small intestine caused by giardia lamblia. The disease is usually asymptomatic though it can present as acute or chronic diarrhea. Giardiasis is a major cause of intestinal infection and Iran is an endemic area of the disease. Despite reports about drug resistance, long course treatment and various side effects, metronidazole is the drug of choice for giardiasis. In this study we investigated in vivo effects of five new derivatives [a-e] of metronidazole [MTZ] on the giardia lamblia trophozoite in infected mice. Giardia intestinalis cysts were isolated from a patient and purified by sucrose gradient method. Fifty Purified cysts were inoculated to mice and after development of infection, the new metronidazole derivatives were given to the mice and results were compared to metronidazole as positive control. Compounds a and b showed desirable antigiardiasis activity and could destroy the cyst and trophozoite of giardia lamblia in mice after both two and four days, but the activity of the other compounds appeared only after 4 days