Staphylococcus eye infection is considered as a difficult medical dilemma because of emergence of highly resistant strains of this bacteria and the increase in its incidence in eye infections.The aims of the present study is to determine the incidence of resistant staphylococcal eye infection in patients of Ibn-Al haitham eye hospital in Baghdad city, isolation and characterization of staphylococcus from infected eyes, and determination the effectiveness of Imipenem alone and in combinations with Ciprofloxacin, Gentamicin, or Rifampicin on isolated Staphylococcus in vitro and in vivo. Sixty six samples were collected from infected eyes of patients in ibn- Al haitham eye hospital in Baghdad for a period between 1/5/2009 to 1/10/2009. Staphylococcus isolates represent 50% of the samples and Staphylococcus aureus represented 13.6% of total isolates. The staphylococcal identification depended on morphological, biochemical test in addition to API staph system. The disc diffusion method was used to test the antibiotic sensitivity of staphylococcal isolates, where 12 type of different antibiotics involved, the following percentage of resistance were found 61%, 46%, 30.7%, 30.7%, 23%, 23%, 23%, 23%, 15%, 15%, 7.7%, 7.7% to the following antibiotics consequently Kanamycin, Cephalexine, Vancomycin, Trimethoprim, Chloramphenicol , Streptomycin, Gentamicin, Ciprofloxacin, Bacitracin, Imipenem, Rifampicin, and Oxacillin. Multiple antibiotic resistance in staphylococcal isolates were found according the following percentage, sensitive to the tested antibiotics 7.6%, resistant to one antibiotic 15.4%, resistant to two antibiotics 23%, resistant to three antibiotics 23%, and resistant to more than three antibiotics 30.7%. In minimum inhibitory concentrations (MICs) study on staphylococcal isolates show the following percentage of resistance 100% resists gentamicin, 46% resistant to imipenem, 46% resistant to ciprofloxacin, while no resistance to rifampicin. Fraction inhibitory concentration FIC values were used to assess the synergism between imipenem and (rifampicin, gentamicin, and ciprofloxacin) and showed that when imipenem combined with gentamicin, imipenem with ciprofloxacin, and imipenem with rifampicin. 81.8% of isolates showed synergistic activity and 18.2% of isolates showed indifference. experimental model of keratitis were used to demonstrate the clinical grading and scoring method to assess the effectiveness of imipenem alone and in combination with (rifampicin, gentamicin, and ciprofloxacin) when used topically after induction of keratitis in rabbit`s eyes by using staphylococcus aureus isolate obtained from infected eye patient. Where 18 rabbits used in this experiment divided into 6 groups. The results showed that the percentage of reduction of clinical progression of bacterial keratitis was 37.5% (significant reduction) when treated with imipenem alone, 35%(significant reduction) when treated with imipenem plus ciprofloxacin, 42%(highly significant reduction) when treated with imipenem plus gentamicin, and 45.3%(highly significant reduction) when treated with imipenem plus rifampicin. Conclusion the combination of imipenem with gentamicin, rifampicin, and ciprofloxacin in vitro has synergistic effect. While in vivo the study with rabbit model suggest that topical use of imipenem alone and in combination with ciprofloxacin, rifampicin, and gentamicin have potential role in healing keratitis caused by staphylococcal infections.