Five 2,10-disubstituted phenoxazines (10-3'-N-bis(hydroxyethyl)amino]propyl]phenoxazine BPP; 10-3'-N-bis(hydroxyethyl)amino]propyl]-2-chlorophenoxazine BPCP; 10-4'-(N-diethylamino)butyl]-2-chlorophenoxazine DBCP; 10-(3'-N-morpholinobutyl)-2-chlorophenoxazine MBCP; 10-(3'-N-piperidinobutyl)-2-chlorophenoxazine PBCP) were studied for their ability of potentiating antibacterial activity of seven antibiotics such as streptomycin, gentamicin, kanamycin, amikacin, spectinomycin, benzylpenicillin and amoxicillin against resistant strains of Escherichia coli, E. coli K12 MG 1655 and E. coli ST 58. All the five phenoxazine derivatives exhibited significant potentiation of antibacterial activity of all the antibiotics up to 16-fold in vitro against both the two bacterial strains studied, except the two penicillins (benzylpenicillin and amoxicillin). The results of present investigations revealed that 2,10-disubstituted phenoxazines (BPP, BPCP, DBCP, MBCP and PBCP) could successfully reverse the multiple antibiotic resistance (MDR) in E. coli K12 MG 1655 and E. coli ST 58, making them sensitive to antibiotics.