This study investigated the effects of rabbit autologous platelet lysates (APL) on the performance of fillers consisting of calcium carbonate ceramic particles (CP) pertinent to new bone formation and repair. Critical-size defects in rabbit femurs and calvaria were filled with CP alone, CP plus APL, and CP plus APL with or without thrombin (THR). After 6 weeks, resorption of CP occurred under all conditions tested in the present study. Compared with respective CP alone controls, addition of APL resulted in significantly higher ceramic resorption, as evidenced by decreased ceramic particle diameter (p < 0.01) and number (p < 0.01) at both defect sites. The presence of THR prevented reduction of both CP diameter and number in the femoral defect sites. Addition of APL to the CP resulted in a significant (p < 0.03) decrease in new bone area at the calvarial sites, but not at the femoral sites; moreover, when THR was added to the CP plus APL fillers, bone formation in the femoral defects was significantly (p < 0.05) reduced. In addition to differences in the respective anatomical and cellular milieu, the biochemical events induced by mechanical loading at the femurs may explain the reduced ceramic particle resorption as well as the enhanced new bone formation when compared with the results obtained at the calvarial defect sites.