Composite scaffolds comprising poly(L-lactid) (PLLA), poly(lactide-co-glycolide) (PLGA) and hydroxyl apatite (HA) are fabricated by a novel method namely high-pressure compression molding plus salt-leaching techniques. A highly densified porous structure is obtained by regulating the pressure, temperature and time of the compression molding. The maximum load of scaffolds formed at 1000 MPa/180 °C/45 min could climb up to a superb level of 71.45 N, 3.5-fold higher than the maximal value (21.7 N) ever reported in the literature; Similarly, the corresponding Young's modulus (6.84 MPa) becomes the highest value to date and comparable to that of the rat cranial bone at 25 °C (~6 MPa). In this regard, such high-pressure structured scaffolds are investigated for applying in cranial defect reparation, while the normal-pressure specimens are employed as a control. By doing the analysis of data derived from SEM, degradation test, cytocompatibility as well as X-ray examination, high-pressure scaffolds not only possess an interconnected 3D network structure with porosity above 80%, but also have excellent in vitro and in vivo performance, including appropriate degradation rate, enhanced cell proliferation and high X-ray radiopacity of 116.1. More importantly, nano-indentation and histological examination show that the defect repaired by high-pressure scaffolds exhibit better biomechanical properties and functionalities than normal-pressure groups, fully suggesting a prominent effect of high pressure on promoting the reparation of defected rat skull.