Lactobacillus (Lb.) casei Lb 28, isolated from gastrointestinal tract of marine fish (Sarda sarda ), produce bacteriocin which has wide spectrum of inhibition against human pathogenic bacteria: S aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Proteus mirabilis, Enterobacter cloacae, Shigella sp, Bacillus cereus, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and penicillin-resistant Streptococcus pneumonia (PRSP). However, no activity was detected on vancomycin resistant Enterococcus faecalis (VRE), Acinetobacter sp. and Candida albicans. The inhibitory activity of bacteriocinogenic Lb. casei Lb28 was eliminated upon treatment with proteinase K, α-chymotrypsin and trypsin but was not affected by lipase and α-amylase. Likewise, the antibacterial activity of crude supernatant fluid was maintained after heating at 121 °C for 20 min, at acidic and neutral pHs (4 – 10). The results obtained in this study revealed that the ability of bacteriocins produced by LAB of marine fish in inhibiting a wide-range of human pathogenic is of potential interest for food safety and may have future applications as food preservative and/or possible antibiotic alternatives.