Objective To prepare a collagen/chitosan scaffold incorporating simvastatin-loaded PLGA microspheres (SIM/COL/CS), which can release simvastatin (SIM) in a sustained manner, and investigate the biocompatibility of the scaffold. Methods Collagen/chitosan scaffolds incorporating SIM-loaded PLGA microspheres were prepared by combining freeze-drying technology and emulsion-solvent evaporation method. The morphology and drug release profile of the scaffolds were characterized by scanning electron microscope and ultraviolet spectrophotometry respectively. The effects of the composite scaffold on the proliferation and viability of the rat bone marrow-derived mesenchymal stem cells (BMSCs) were assessed by Cell Counting Kit 8 (CCK-8) and Live/Dead cell imaging kit separately. The osteoinductive effect of the scaffold on BMSCs was evaluated by alkaline phosphatase (ALP) activity assay and alizarin red S staining. Results The composited scaffolds exhibited an interconnected porous structure and the PLGA microspheres were tightly integrated within the matrix. Besides,the SIM exculpated in the scaffold was released in a sustained manner for up to 27 days. CCK-8 assay showed that although there was no difference in cell number between the COL/CS and SIM/COL/CS groups on days 1, 3 and 5, cell number in the SIM/COL/CS group was significantly higher than that in the COL/CS group on day 7. Live/dead cell staining indicated the viability of the BMSCs on both COL/CS and SIM/COL/CS were good and few dead cells (red) was found. Moreover, both of the ALP activity and calcium deposit in the SIM/COL/CS group were significantly higher than those in the COL/CS group. Conclusion COL/CS scaffolds containing SIM-loaded PLGA microspheres for controlled SIM delivery can be successfully prepared by combining freeze-drying technology and emulsion-solvent evaporation method. The novel SIM-loaded COL/CS scaffold can promote both the proliferation and osteogenic differentiation of BMSCs and has great application potentials in bone repair.