The antimicrobial activity of phycocyanin extracted from Anabaena oryzae SOS13 was assayed using agar well-diffusion assay, the concentration inhibiting 50% bacterial growth and minimum inhibition concentration (MIC) against 4 pathogenic bacteria. The mode of action of phycocyanin was xplored on gram positive and gram negative bacteria using electron microscopy (SEM, TEM). The results showed that phycocyanin from Anabaena oryzae SOS13 has α and β subunit corresponding to 14 and 24 kDa, with an isoelectric point near pH 6 and 50 % hydrophobic amino acid content. Agar well diffusion assay revealed that Anabaena phycocyanin induced inhibition zones against Bacillus cereus and Staphylococcus aurous (G+) and Escherichia coli and Klebsiella pneumonia (G-) with no specific difference among G- and G+ while benzyl penicillin is ineffective against the second. Anabaena phycocynin achieved IC50 values lower than Spirulina phycocyanin and benzyl penicillin against the four studied bacteria. Anabaena phycocyanin (100 µg/ml)-treated cells (B. cereus and K. pneumonia) showed signs of irregular wrinkled outer surface, fragmentation, adhesion and aggregation of damaged cells or cellular debris and cell wall separation from cell membrane. Anabaena phycocyanin has antibacterial activity, against four pathogenic bacteria, greater than Spirulina phycocyanin or benzyl penicillin and other three antibiotics. It exerts its action through affecting the bacterial cell walls and membranes.