OBJECTIVE: Infectious diseases such as typhoid fever lead to the formation of free radicals which can damage the body. Many medicinal plants have antioxidant molecules that neutralize free radicals. The present work evaluated the antioxidant activity and histopathological effects of the dichloromethane fraction of Dichrocephala integrifolia in Salmonella typhi-infected rats. METHODS: The S. typhi-infected rats concurrently received daily doses of D. integrifolia extract at doses of 25, 50 and 100 mg/kg body weight or ciprofloxacin (5 mg/kg body weight) for 15 days. Body temperature was measured daily during infection and treatment periods. At the end of treatment period, the animals were sacrificed and biological responses including hematological parameters, superoxide dismutase and catalase activities, and glutathione, malondialdehyde and nitric oxide concentrations were evaluated. RESULTS: The elevated body temperature induced by infection was significantly decreased in animals treated with 25, 50 or 100 mg/kg of the extract. Platelet levels decreased slightly in infected rats, while treatment with the dichloromethane fraction of D. integrifolia significantly increased platelet levels; this response was greater than that elicited by ciprofloxacin. The doses of 50 and 100 mg/kg of the dichloromethane fraction of D. integrifolia notably decreased monocyte and neutrophil values. Activity of superoxide dismutase and catalase and levels of glutathione in the tissues of treated animals were increased significantly (P < 0.01), while malondialdehyde and nitric oxide levels were significantly decreased (P < 0.01), following treatment with the dichloromethane fraction of D. integrifolia. CONCLUSION The results of this study show that the dichloromethane fraction of D. integrifolia has protective effects against a series of pathological conditions initiated by oxidation and tissue damage in the course of a S. typhi infection.