In this work we focused on the synthesis of two new macrocyclic Schiff bases: (III) , ( IV), (VI) containing nitrogen â€“ oxygen donor atoms were synthesized by condensation of intermediate compounds: 1,6- bis (2- formylphenel) hexane (I)and Î±,Î±â€™-bis (2-carboxyaldehyde phenoxy) xylene(II) with 4,4'-Diamino-diphenylmethane and 4-Aminophenyl sulfone. Also new open Schiff bases (V) which were prepared by condensation of benzylhydrazidewith 1, 6- bis (2- formylphenel) hexane (I). Identification of these macrocyclic Schiff bases: 1,16-di aza-3,4,13,14-tri phenyl-17,25 -di phenyl methane-5,12-di oxacyclo penta-icozane-1,15-diene(III), 1,16- di aza-3,4, 7, 10, 13,14-tri phenyl-17,25 -di phenyl methan-5,8- di oxacyclo penta-icozane-1,15-diene. (IV).1,16-di aza- 3,4,13,14-tri phenyl-17,25 -di phenyl sulphide-5,12-di oxacyclo penta-icozane-1,15-diene(V), And N',N'-(2,2'-(hexane-1,6- bis(oxy))bis(2,1-phenylene))bis(methanylidene) dibenzhydrazide. (VI).The Schiff bases were checked by different spectral technique (LC-MS, 1H-NMR, IR, elemental analyses). The new Schiff Bases were studied for antibacterial activities against (Bacillus subtilis and Staphylococcus aureus) are Gram positive and (Salmonella typhi and Escherichia coli) are Gram negative. The ligands were exhibited a variable activity of inhibition on the growth of the bacteria.