In trial to investigate the effect of experimentally Pasteurella multocida , ofloxacin, Grape seed extract and both together onhistopathological changes in rabbits, Fifty weaned rabbits were divided into five groups; control negative (I), control positive (II), ofloxacin treated (III), GSE treated (IV) and combined treated groups (V). The result of histopathological changes of Pasteurella infected group showed severe peribronchitis and congested blood vessels as well as severe lymphocytic infiltrations and compensatory emphysema in lung. Liver revealed massive lymphocytic infiltration along with fibrosis around the hepatic area. Diffuse degeneration of hepatocytes and focal necrosis were also observed. Kidneys showed degeneration of renal tubules and focal interstitial aggregations with lymphocytes. The animals of group III (O) and group IV (G), showed mild to moderate lesions. The group V (O+G) showed pronounced improvement in tissues. It could be concluded that using both ofloxacin and GSE had a good effectiveness in treatment of Pasteurellosis in rabbits.