Abstract: Thiazolidinediones (TZDs) acts by stimulating PPAR that improves glycaemic control by decreasing insulin resistance. Although the use of Thiazolidinediones had long been associated with cardiovascular risk factors but it is commonly used as a potent anti-diabetic. The use of Thiazolidinediones (TZDs) in the management of type 2 diabetes mellitus (T2DM) had been associated with an increased risk of peripheral oedema. Mainly class include Ciglitazone, Rosiglitazone, Troglitazone and Pioglitazone. Mannich reaction have proved to be more effective and leads to generation of new compounds which are less toxic but pharmacologically more active than their parent drugs. Mannich Bases of Pioglitazone were synthesized by making use of the abstractable hydrogen in the Pioglitazone and it was aminomethylated using DMF as solvent. The subjected mixture was stirred with continuous addition of formaldehyde and was refluxed to yield various potent biological mannich bases of Pioglitazone. These considerations have provoked Mannich bases of secondary amine by Mannich reaction.