Abstract: The present study was to investigate the comparative efficacy of ceftriaxone and a fixed dose combination of ceftriaxone plus sulbactam along with VRP1034 (Sulbactomax) in cerebrospinal fluid (CSF) of meningitis induced rat model. Eighteen rats were divided into three groups of six rats each. Meningitis were induced by MRSA strain (log 106 cfu mL-1). Group I was infected group; whereas group II and III were ceftriaxone and sulbactomax treated groups. Drugs were analyzed in CSF by high performance liquid chromatography. Some biochemical parameters were studied in infected and treated groups. Present results showed that the mean level of ceftriaxone drug concentration was increased significantly in sulbactomax treated group in comparison to ceftriaxone alone treated group. Glucose level was increased in sulbactomax treated group as compared to ceftriaxone alone treated group. The levels of protein, calcium and phosphorus were significantly lowered in both treated group as compared to infected group. These biochemical parameters were decreased along with increased glucose level in sulbactomax treated group in comparison to ceftriaxone alone treated group. Present findings concluded that sulbactomax enhanced the penetration rate in CSF than ceftriaxone alone due to VRP1034. It plays a therapeutic role in crossing blood brain barrier and helps in prevention of bacterial meningitis infection.