Seventy of commercial broiler chicks of 2 week old ages were used to study the efficiency of either or both Danofloxacin and Tilmicosin in experimental chronic respiratory diseases (CRD) infection. The latter was induced by simultaneous infection of both mycoplsama gallisepticum with E.coli. Experimental groups divided into 7 groups (Gps) of 10 chicks. Gp. 1 was left without treatment, gp. 2 was orally given 2 ml distilled water, gp. 3 received 0.1ml/kg B.wt danofloxacin, gp. 4 received 1.2 ml/kg B.wt from tilmicosin and gp. 5 were inoculated with 0.2 ml inoculum of both mycoplasma gallisepticum (MG) and E.coli (O78) intra-tracheally route. Meanwhile  Gp .6 and 7 were the experimental groups where the infected chicks received 0.1ml/kg B.wt danofloxacin and 1.2 from tilmicosin orally for five consecutive days after the clinical signs appeared by 24 h respectively. Necropsy was performed weekly; clinical signs and gross lesions were recorded. Specimens from liver, heart, lungs, kidneys, air sac, brain, spleen, bursa of fabricus were collected from all the necropsied chicks. In gp.5, the main clinical signs were severe depression, anorexia and respiratory signs, while macroscopically were septicemic lesions were seen 1 and 2 weeks post inoculation (PI) together with fibrinous perihepatitis, pericarditis and airsacuilitis. Microscopically, the liver showed several areas of central cavitations surrounded with a zone of coagulative necrosis with perihepatitis represented by thickening in the hepatic capsule by fibrinous exudates and leukocytes infiltrations. The heart showed thickened pericardium with serofibrinous exudate entrapping macrophages, lymphocytes and few heterophils.  The trachea showed focal areas of necrosis or ulceration with extensive replacement of the mucosa with leukocytes.The lungs revealed more serious lesions which represented by severe bronchitis and focal pneumonia.The air sacsshowed heterophils and mononuclear cells infiltrations, particularly at the first 2 weeks. The spleen showed necrosis and depletion of lymphocytes from white pulp. Meanwhile in gp 6, the danofloxacin were alleviated the severity of the lesions and in gp. 7 tilmicosin complete absent of the lesions.