Objectives: Ganoderma lucidum, a traditional Chinese mushroom, has been widely used for the management of antibacterial infection and nutrition. This study was conducted to investigate the protective effect of Ganoderma lucidum methanol extract against MRSA infection in vitro and in vivo in case of made special diet for albino rates. Methods:  Ganoderma lucidum was collected then form extracted using methanol and characterized using GC-MS. In vitro assay to evaluate anti-MRSA activity was done using Agar well diffusion method with MIC determined. In vivo,  total of 32 male and female albino rats of 6-8 weeks with a body weight of (115 – 120) g were divided into four groups with 8 rats in each: negative control, positive control injected IP with 200 micro of  MRSA (8*10^8 CFU/mouse) and  2 groups have injected IP with 200 micro of  MRSA (8*10^8 CFU/mouse) with G. lucidum methanol extract dose of (125 and 250 mcg  respectively) for 3 weeks, blood samples and lungs were collected for examination. Results: Treatment of albino rats with Ganoderma lucidum methanol extract reduced the histological changes due to lung inflammation induced by MRSA infection and significantly reduced increasing in the lactate dehydrogenase (LDH) levels. Also, it shows a good antibacterial effect against MRSA colonies growth which supports the antibacterial therapeutic effect of G. lucidum.Conclusion:Present study concluded that G. lucidum methanol extract has potent antibacterial effect against MRSA infected albino rats, and it's effective as protective against lung inflammation induced by MRSA infection.