Purpose: The effectiveness of rapid maxillary expansion is adversely affected by failure and relapse. It is important to identify key factors that increase new bone formation and improve bone remodeling of midpalatal sutures to improve the stability and effectiveness of this commonly used orthodontic procedure. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in modulating osteogenesis and bone resorption in long bones. This study was designed to explore the function of PPARγ in bone remodeling and tissue engineering of midpalatal sutures. Materials and Methods: Pioglitazone, a PPARγ agonist, and osteoclast PPARγ knockout mice were used to explore the impact of PPARγ activation and inactivation, respectively, on bone remodeling in a mouse model of midpalatal suture expansion (MSE). Histologic analysis including staining with hematoxylin-eosin, tartrate-resistant acid phosphatase, and alkaline phosphatase was used to evaluate tissue remodeling. Reverse-transcriptase quantitative polymerase chain reaction was used to measure gene expression. Results: Pioglitazone decreased new bone formation after MSE. This was accompanied by an increased amount of osteoclasts and expression of genes promoting osteoclastogenesis, as well as a decreased amount of osteoblasts and expression of genes promoting osteoblastogenesis in midpalatal sutures. Conversely, osteoclast PPARγ knockout mice increased new bone formation and decreased the amount of osteoclasts and expression of genes promoting osteoclastogenesis. Conclusion: In the process of bone remodeling after MSE, PPARγ, particularly in osteoclasts, is an important regulator of osteoblast and osteoclast homeostasis and bone remodeling in midpalatal sutures. Blockade of PPARγ might be an effective strategy to improve stability and decrease relapse in the practice of rapid maxillary expansion. Keywords: bone remodeling, midpalatal suture expansion, osteoblast, osteoclast, peroxisome proliferator-activated receptor gamma