A series of methyl 3-(2-amino-2-oxoacetyl)-6-chloro-1-methyl-1H-indole-5-carboxylate were screened for their anti-microbial activity against bacteria S.aureus. These compounds have showed moderate and very good antimicrobial activity. The Quantitative Structure Activity-Relationships (QSAR) study on the indole series was made using lipophilic, electronic and steric parameters. Several statistical expressions were developed and best models were validated. The studies confirm that the antimicrobial activity is dependent on selected lipophilic, electronic and steric parameters.The QSAR study provides important structural insights in designing of potent antimicrobial agents.