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The experiment was done to examine the effect of sulfanilamide and HSV on hematological and some biochemical parameters in addition histopathological changes in male rabbits, this experiment was carried out on 18 male rabbits, these animal acclimatized for one week before then divided into three groups (6 rabbits in each). First group as control group were given of dimethyl sulphoxide( 0.5 ml) I.P daily, second group were treated withsulfanilamide drug (195 mg/kg) I.P daily, while, third group weregivenof HSV(83.86 mg/kg) I.P daily. The treatment continues for three weeks, the results showed significantly reduction in RBCs, Hb, PCV, this reduction was companied by a significant decrease MCH, MCHC, as well as a significant decrease in Platelet count, while observed significantly increase in AST and ALT activities also a significant increase in total cholesterol, the study produced a significant increase in urea and creatininewhereas significantly decrease in total protein and albumin associateda significant increase in globulin, histopathological study showed congested in portal vein and periportal fibrosis, while in kidney dilated cortical tubules and atrophy glomeruli were noted in the male rabbits treated with sulfanilamide, from our results the group treated with HSV showed improvement in hematological and biochemical parameters, while ameliorated the histopathological changes in liver and kidney were showed. Concluded theadministrationofsulfanilamide cause to several adverse effects while the administration of HSV attenuation of this impact. [ABSTRACT FROM AUTHOR]