A series of some new benzoxazines derivatives have been synthesized using conventional method and solvent-free microwave thermolysis. It was observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of benzoxazines when compared with conventional reaction in a solution phase. All the compounds synthesized were tested for anti-inflammatory activity. Compound 3f, 3h, and 3l showed 74.87, 70.39, and 71.89% of inhibition in rat paw edema, 57.38, 54.27, and 55.47% of protection against acetic acid induced writhings, and 0.08, 0.17, and 0.17 of severity index (SI), respectively compared to 82.33, 63.06, and 1.0 values of ibuprofen. The study showed that these compounds are good and safe anti-inflammatory agents and can be used to develop potent and safe anti-inflammatory agents.