Samples form lungs, trachea and air sacs were collected from 40 turkey poults suffering f rom respiratory signs for bacteriological examination for isolation and identification mycoplasma spp. The results revealed, 18 (45%) samples were positive (+ve) for mycoplasma spp. Antibiogram study of isolates revealed that pefloxacin and tiamulin was effective against mycoplasma. A total of 40, one-day old poults provide free from mycoplasma infection were divided into 4 equal groups. 1 st group healthy negative (-ve control) 2 nd , 3 rd & 4 th groups were artificially infected with Mycoplasma gallisepticum (MG), 2 nd group infected non treated (+ve control), 3 rd group infected treated with 5 mg pefloxacin / kg bwt in drinking water for 5 successive days and 4 th groups was infected treated with 25mg tiamulin/kg bwt in drinking water for 5 successive days, At 1 st and 10 th days post treatment 5 poults from each group were sacrificed for record lesion scores % and two blood samples were taken from each poults for hematobiochemical parameters study. Poults infected with Mycoplasma gallisepticum revealed loss of appetite, depression, sneezing, conjunctivitis, frothy exudation in eyes, air sacculitis 7 ( 70 % ), pericarditis 7 (70 % ), perihepatitis 8 (80 % ) & mortality rate 4 (40 ( % beside induces significant increase in WBCs, AST ALT, ALP uric acid, creatinine and significant decrease in weight gain. Phagocytic %, index, killing % IgA, IgG, IgM, T protein, albumin and globulin. Medication mycoplasma gallisepticum by tiamulin or pefloxacin revealed disappears of clinical signs, reduced mortality rate to10%, mild lesion scores re-isolation rate of Mycoplasma gallisepticum from poults treated with pefloxacin was (20%) and (10%) for tiamulin beside improve in hematobiochemical parameters and returned to nearly normal level at 10 th day post treatment. It could be concluded that pefloxacin and tiamulin was effective in treatment Mycoplasma gallisepticum in poults and ameliorate severity of its lesions besides improving adverse effect in hematobiochemical parameters.