Purpose: The purpose of this study is to histologically and histomorphometrically evaluate the effect of PLGA on bone regeneration compared with bone graft material. Methods: The experimental study was conducted in 10 rabbits with 2 different healing periods of 2 and 4 weeks. Following surgical exposure of the calvarium, 4 circular bone defects with a diameter of 4.6mm were formed. Rabbits were divided into control group, test groups I, and II. 10 defects assigned to the test group Ⅰ were grafted with Nu-oss and other 10 defects assigned to the test group II were grafted with PLGA. The rest of the defects were in the negative control group. At 2nd and 4th week after surgery, 10 rabbits were sacrificed through intracardiac perfusion and then specimens were obtained. Histological analysis was performed following staining with trichorme and transversal sectioning of the calvarial bone. Results: A group which used PLGA showed tissue reactions characterized by severe inflammation, rather than distinctive new bone formation. Conclusions: The present experimental investigations have failed to prove any beneficial effects of PLGA. PLGA used in this study exhibited foreign body reactions and a less favorable pattern of new bone formation in comparison to control group. Conclusion: PLGA did not function as scaffold. Further investigations of many types of micro PLGA that could improve its potential in GBR procedures are needed.