2H-1,4-pyridooxazin-3(4H)-one was synthesized by condensation of 2-amino-3-hydroxy-pyridine with chloroacetylchloride by using standard procedure . Esterification with ethylchloroacetate and further condensation with hydrazine hydrate produced hydrazide of 2H-1,4-pyridooxazin-3(4H)-one. Schiff base derivatives of 2H-1,4- pyridoxazin-3(4H)-one were synthesized by the acid catalyzed condensation 2-(3-oxo-2,3-dihydro-4H-1,4- pyridoxazin-4-yl)acetohydrazide with various benzaldehyde derivatives. Schiff base derivatives were characterized by FT-IR, 1H-NMR. All compounds were screened for anti-inflammatory activity by carrageenan induced edema in mice paw against diclofenac sodium as a standard drug. The activity reflects their ability to provide protection (45.00-70.00%). The safety of these schiff base derivatives are reflected by toxicity studies.