In order to establish the role of various essential and trace element complexation on the antibacterial activity of various macrolide antibiotics, the synergistic or antagonistic behavior of erythromycin metal complexes have been studied and compared with the parent drug. Metal complexes of erythromycin with magnesium, calcium, chromium, manganese, iron, cobalt, nickel, copper, zinc and cadmium have been investigated for their antibacterial activity and compared with erythromycin by observing the changes in minimum inhibitory concentration (MIC) and by measuring the zone of inhibition of complexes against both Gram-negative and Gram-positive microorganisms. Various microorganisms used were Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Salmonella typhi, Proteus vulgaris, Shigella dysentary, Klebsiella pneumoniae and Staphylococcus epidermidis. For MIC observation, serial dilution method was employed and zone sizes were determined by diffusion disk method. Our investigations reveal that formation of erythromycin complexes result in synergistic effect i.e., antimicrobial activity of complexes of erythromycin increases with respect to parent erythromycin drug and MIC of drug metal complexes decreased.