In the present paper, a quantitative structure activity relationship (QSAR) has been carried out on a series of 2-methyl and 2-aminobenzimidazole derivatives to identify the lipophilicity requirements for their inhibitory activity against bacteria Sarcina lutea. The tested compounds displayed in vitro antibacterial activity and minimum inhibitory concentration (MIC) was determined for all compounds. The partition coefficients of the studied compounds were measured by the shake flask method (log P) and by theoretical calculation (Clog P). The relationships between lipophilicity descriptors and antibacterial activities were investigated and the mathematical models have been developed as a calibration models for predicting the inhibitory activity of this class of compounds. The models were validated by leave-one-out (LOO) technique as well as by the calculation of statistical parameters for the established models. Therefore, QSAR analysis reveals that lipophilicity descriptor govern the inhibitory activity of benzimidazoles studied against Sarcina lutea.