The current study was conducted to investigate the impact of Mentofin^® in protection of the respiratory system of broiler chickens challenged with Mycoplasma gallisepticum (MG) strain. One hundred and five – one day old chicks were randomly divided into three equal groups (35 chicks /group) and reared in isolated rooms. Group (A) MG challenged, Group (B) was treated with Mentofin^® and MG challenged and Group (C) control –ve group (not challenged with MG and not treated with Mentofin^®). At 1^st week of age, an intra-tracheal challenge of the birds with MG strain (containing 1 x 10⁶cfu/ mL/bird) was given to A and B. Mentofin^® was administered orally for 6 days, beginning from 8^th day of ages to 13^th day of ages. Tracheal and lung samples for histopathological examination were collected from chicken at 9^th day to 14^th day of age and at 28^th day of age. In MG-challenged birds (group A) histopathological lesions included mucosal hyperplasia, mucus accumulation, tracheal deciliation, inflammatory cells infiltration and goblet cell hyperplasia in tracheal tissues, moreover, congestion and pneumonic foci in lung tissues. The histopathological lesions of birds treated with Mentofin^® and MG challenged (group B) revealed a significant reduction in histopathological lesions in tracheal and lung tissues. Mentofin^® was able to  reducing  respiratory  problems, and  recommended  to be used  as a  prophylaxis  treatment  and supportive  treatment  with  antibiotic  in  cases of  mycoplasma gallisepticum infection.