The purpose of this study was to develop a novel β-Tricalcium phosphate (TCP) /Poly (D,L-lactic-co-glycolic acid) (PLGA) composite scaffold loaded with rapamycin that can regulate the activity of osteoblasts and osteoclasts for lumbar fusion. The TCP/PLGA composite scaffold was fabricated by cryogenic 3D printing techniques and then loaded with rapamycin in situ. The structural surface morphology of the composite scaffold was tested with scanning electron microscope (SEM). To evaluate the biocompatibility of the composite scaffold in vitro, bone marrow mesenchymal stem cells (BMSCs) were cultured on the TCP/PLGA composite scaffold slide and tested with Live/dead viability Kit. The effect of rapamycin on osteoclast and osteoblast was studied with staining and Western Blotting. The in-vitro results showed that the rapamycin-loaded TCP/PLGA composite scaffold showed good biocompatibility with BMSC and released rapamycin obviously promoted the osteoblast differentiation and mineralization. In vivo study, the TCP/PLGA composite scaffold loaded with rapamycin were implanted in lumbar fusion model and study with Micro-CT scanning, HE, Masson and immune-histological staining, to evaluate the effect of rapamycin on bone fusion. The in vivo results demonstrated that rapamycin-loaded TCP/PLGA composite scaffold could enhance bone formation by regulating osteoblast and osteoclast activity, respectively. In this study, the TCP/PLGA composite scaffold loaded with rapamycin was confirmed to provide great compatibility and improved performance in lumbar fusion by regulating osteoblastic and osteoclastic activity and would be a promising composite biomaterial for bone tissue engineering. This article is protected by copyright. All rights reserved.