The sponge-microbial association is a potential chemical, ecological phenomenon, which provides sustainable source of supply for developing novel pharmaceutical leads. The present study was carried out to investigate the in vitro antimicrobial activity of sponge associated actinomycetes and actinomycetes isolated from marine soil. Sixty three marine actinomycetes strains were isolated from the sponge and soil samples collected from two different stations from Arabian sea, south west coast of India. The counts of actinomycetes were found maximum in sponges during south west monsoon season. The antimicrobial screening showed that, five Streptomyces sp. exhibited antimicrobial activity against eye pathogens, antibiotic sensitive and resistant bacterial pathogens.