Meningitis is common in tropical areas and also in Egypt and has a world-wide distribution This study evaluated the potential role of CSF TNF α in diagnosis and differential diagnosis of acute meningitis (bacterial versus aseptic meningitis). This case-control study was conducted between Ain Shams University Tropical Medicine Department and Embaba Fever Hospital. Fifty patients with suspected meningitis were recruited during from January 2014 to June 2014. They were divided according to culture results into 2 groups: GI: 40 patients with acute bacterial meningitis (proved by CSF culture), G2: 10 patients matched according to age and sex with clinical sings of CNS infection but without laboratory evidence of bacterial origin, (Suspected cases, and negative culture). Both groups were subjected to thorough history taking, full clinical examination, and laboratory investigations including CSF analysis & CSF TNF was measured by ELISA. The results showed a highly significant difference between cases and control regarding CSF TNF (P=0.00). The criteria's of diagnostic validity test was 100% for all at cutoff ≥275ng/ml and ≤700ng/ml with 100% specificity and sensitivity. A significant correlation between CSF-TNF and each of ESR (P=0.003) & CSF cells (P=0.015), without significant correlation regarding other parameters (P>0.05).