The present invention provides novel liposomal formulations of polymyxin B and pharmaceutical compositions thereof useful for the treatment of bacterial infections. The liposomal formulation comprises a lipid component formed as vesicles each having a minimum size of at least 500 nm and polymyxin B encapsulated in the vesicles. The present invention also provides a drug delivery system that comprises a plurality of liposomes encapsulating a polymyxin B therein, where the liposomes have a minimum vesicular size of at least 500 nm. The liposomes comprising the drug delivery system are useful to increase efficacy of a treatment for a bacterial infection by increasing bioavailability and distribution of the polymyxin B within the subject.