Aim: The aim of the present study is to synthesis and screening the anti-inflammatory effect quinoxaline-2-3-dione tethered 2-amino-5-substituted-1,3,4-thiadiazole derivatives. Method: Thus various 2-amino-5-substituted-1,3,4-Thiadiazole were added to a mixture of formaldehyde and 75% ethanol along with quinoxaline-2,3-dione then irradiated for 4 minutes at 250 watt. All the title compounds were tested for their anti-inflammatory activity of the synthesized compounds was evaluated by Carrageenan induced paw edema method in rats. The activity was studied at 200 and 400 mg/kg b.w., p.o. and their effects were measured at 30, 60, 120 and 180 min. Result: Anti-inflammatory activity of synthesized compounds was tested by Carrangeenan induced paw edema method in rats standard drug used for the study was Diclofenac sodium. The methoxy, chloro and bromo substitution in three derivatives showed significant anti-inflammatory activity when compared to standard. The hydroxy, nitro groups showed mild activity when compared to standard. Conclusion: A novel series of quinoxaline 2,3- Dione derivatives has anti-inflammatory activity so supplementary exploration has been needed to establish other pharmacological performance of these derivatives and in future it would be a most promising and leading derivatives for several ailments.