The peroxisome proliferator-activated receptor gamma (PPAR-c) is member of a large family of ligandactivated nuclear transcription factors. The first compounds reported as high-affinity PPAR-c agonists were a class of antidiabetic agents known as thiazolidinediones or ''glitazones''. Quantitative structure activity relationship (QSAR) analyses used to understand the structural factors responsible for PPAR-c agonistic activity of some thiazolidinedione derivatives. Several pharmacophore-based models indicated the importance of steric, hydrophobic, and hydrogen bond acceptor groups to agonistic activity. The 3D-QSAR analysis was carried out by PHASE program and a statistically reliable model with good predictive power (r 2 = 0.9702, q2 = 0.8216) was achieved. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may helps in the design and development of potent thiazolidinedione derivatives as antidiabetic agents.