This work studied the effect of sub-chronic DDT exposure on the course of experimental giardiasis and efficacy of its treatment. A total of 160 mice were divided into six groups: G1: 30 mice received DDT and infected with Giardia lamblia. G2: 30 mice received DDT, infected and treated with tinidazole (TNZ). G3: 30 mice infected with Giardia. G4: 30 mice infected and treated with TNZ. G5: 30 mice received DDT only. G6: 10 mice served as normal control. Mice were sacrificed at 7, 14, 21 & 28 days P.I. All groups were subjected to cyst count/2 hours collected stool, trophozoite count in intestine, histopathological examination of small intestinal section and avidin biotin peroxidase technique for local IgA staining. Also, IFN-gamma was measured in sera. DDT caused early shedding of many cysts and increase in trophozoite counts for a long time, decreased intra epithelial lymphocytes, low levels of IgA & IFN-gamma and severe histopathological changes in intestinal sections in G1 as compared to G3. Also, DDT reduced the efficacy of TNZ treatment in G2 as compared to G4. The results strongly support the immunomodulating effect of DDT on experimental giardiasis that might be responsible for persistence of infection, resistance to treatment and re-infection in DDT exposed persons.