A B S T R A C T Doxorubicin (DOX ) is an anthracycline derivative antibiotic, used as anticancer agent, it causes generation of free radicals and induces oxidative stress, associated with cellular injury and participate in hepatonephrotoxicity in normal human cells .The protective effect of Spirulina Platensis (SP) , a filamentous blue green algae , on Doxorubicin induced oxidative stress and hepatotoxicity was evaluated in male rats. Oral administration of water extract of Spirulina (1000 mg/kg/b.wt) for six weeks following an acute toxic dose of Doxorubicin ( 1.0 mg/kg/b.wt) , reduces the hepatotoxicity and attenuates doxorubicin-induced stress .The post-treatment with Spirulina reduces the activity of Liver marker enzymes such as serum alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Renal function disorders represented by urea. The ratio of decrease were lower in the first three weeks if compared with the last three weeks. On the other hand, Oral administration of Spirulina extract for six weeks following an acute toxic dose of Doxorubicin, led to an obvious increase in the activity of antioxidant Parameters including Catalase ( CAT ) and Super Oxide Dismutase ( SOD ). The results clearly demonstrate that Spirulina treatment augments the antioxidants defense mechanism in Dox induced toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.