Abstract: We had reported microwave assisted synthesis of 2-(3-(2-(1,3-dioxoisoindolin-2-yl) acetamido)-4-oxo-2-phenylthiazolidin-5-yl) acetic acid derivatives 7(a-l) by cyclo-condensation of (E)-N'-substituted benzylidene/methylene-2-(1,3-dioxo isoindolin-2-yl) acetohydrazide 6(a-l) with mercaptosuccinic acid. The newly synthesized compounds were evaluated for anti-inflammatory activity using in-vitro and in-vivo models. The tested compounds had shown promising anti-inflammatory activity in both the models. The aliphatic groups (-CH3, C2H5) on thiazolidinone ring showed better anti-inflammatory activity than substitution of bulkier group (substituted phenyl and heteryl) on thiazolidinone when compared to diclofenac. The electron donating polar groups (4-methoxy phenyl and furyl group) on thiazolidinone ring have also shown good activity when compared to diclofenac. The selected compounds, which have shown better activity, were studied for ulcerogenic toxicity and have shown good gastrointestinal safety profile.