This present work deals with the synthesis, characterization and biological screening of some novel Schiff bases of thiazole derivatives. Ethyl-2(2-amino thiazole-4 yl) glyoxylate (I) react with 2, 5-dimethyl tetrahydro furan gave N-pyrol derivatives (II). Equal mole of (II) and hydrazine hydrate were heated for 10 minutes. It gave mono hydrazine derivatives (III) and when 1 mole of (II) and 2 mole of hydrazine hydrate were refluxed for 3 hours, it gave dihydrazine derivatives (IV). Equal mole of mono hydrazine derivatives (III) and aromatic aldehyde (one mole of dihydrazine derivatives (IV) and one mole of aromatic aldehyde) are refluxed for 10 minutes, it gave pale yellow mono and tri Schiff base derivatives. When (I) was directly reacted with hydrazine hydrate it gave (V). Compound (V) contains both 2-thiazole amine and hydrazine active sites for Schiff base formation. But when (V) was treated with aromatic aldehyde, hydrazine active site form solid Schiff base very fast, because in low temperature 2-thiazole amine get stable by amine emine tautomerism. This is conformed by HNMR (Ar-NH2 proton peak is single let only). The chemical structures of synthesized compounds were conformed by MASS, IR and H-NMR spectral studies. The synthesized compounds were (25, 50 and 100 μg/mL) screened for antimicrobial activity by paper disc diffusion method.