TYPHOID fever a food-borne disease caused by Salmonella species, is a worldwide prevalent disease. In endemic areas, children are at highest risk owing to weaning from passively acquired maternal antibody and lack of acquired immunity. Several studies have been done to clarify the pathogenesis and underlying immune aspects of typhoid fever. The Objective is to study the changes of some proinflammatory cytokines in plasma of children and adults with typhoid fever and resistance to therapy. This study included 128 cases from which 34 consecutive children and adult admitted to Benha Fever Hospital with proven diagnosis of typhoid fever patients with typhoid fever resistant to combined therapy with Ciprofloxacin and Cefotax in addition to Zithrokan and Zantac have higher plasma levels of IL-6 and TNF-alpha. Toxic look, constipation and splenomegaly may be considered as indicators of drug resistance. Study of changes in the levels of some cytokines may offer a new dimension in the assessment of the clinical efficacy of antimicrobial therapy