The present study was to evaluate anti-leukopenia and antioxidant effects of cranberry extract(222mg/kg.b.w, orally)in 400mg/kg.b.w., orally benzene and/or 20mg/kg.b.w., I.P 5-Flourouracil-induced leukopenia rats. Two weeks after induction of leukopenia in rats, cranberry extract was administrated for 30 consecutive days. Onthe31thday, the rats were sacrificed for the estimation of hemoglobin (Hb%), complete blood cell count Leucocyte (WBC) and platelet count (PLT),as well as biochemical parameters; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lipid peroxides (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, p53gene expression, nitric oxide (NO) and tumor necroses factor-alpha (TNF-alpha). The results of this study showed that administration of cranberry extract to leukopenia induced rats demonstrated a significant (P<0.01) increase in Hb%, WBCs and PLT as well as a significant (P<0.01) improvement in biochemical parameters and life span as compared to benzene and/or 5-Flourouracil control rats. The histological examinations of this study revealed damage and degeneration in the lung of benzene and/or 5-Flourouracil treated rats. Also, lung of cranberry treated rats showed significant improvement and protection against benzene and/or 5-Flourouracil harmful effect. On the other hand, the results clearly suggested that the oxidative stress of benzene was higher than 5-Flourouracil. Industrial relevance. Our observations have clearly demonstrated that the cranberry extract has significant antioxidant and anti-leukopenia activity due to presence of phenolic compounds. Cranberry extract possessed a capability to inhibit the lipid peroxidation and activate the antioxidant markers (GSH, SOD and CAT) in leukopenia-induced by 5-Flourouracil and benzene in rats. Also, industrial relevance of the present results showed that cranberry extract can be used as an antioxidant and anti-leukopenia therapeutic agent and deserves clinical trial in the near future as an adjuvant therapy in leukopenic patients. This could serve as a stepping stone towards the discovery of newer safe and effective antitumor agents.