Animal models are an essential pillar of orthopaedic research. Rodents, in particular, have played a pivotal role in developing our current understanding of bone mechanobiology, but they lack the Haversian systems found in human bone. For studies of mechanobiology and in line with FDA recommendations, researchers are turning to larger animal models, like rabbits, which naturally exhibit intracortical remodeling. Our group has developed a non– invasive, in vivo rabbit tibial loading model to establish the relationships between applied load, strains, microdamage accumulation, and bone remodeling. To capture the strain environment, we require a validated computed tomography (CT)–based finite element (FE) model of the rabbit hindlimb. To this end, we first established the density–elasticity relationships for rabbit hindlimb bones. By using well defined experimental boundary conditions for in silico replication, we were able to optimize the density–elasticity power law constants such that the resulting FE models provided strain predictions that were strongly correlated with experimental measurements (0.85 ≤ R² ≤ 0.96). With the ability to accurately assign heterogeneous material properties, the derived relationships were used in CT–based FE models of the rabbit hindlimb. Early findings revealed that FE strain predictions were exceptionally sensitive to the assumed force vector orientation, and increasing the model complexity would be futile. Instead, we developed an experimentally informed optimization approach to determine the individual force vector orientations that minimized the error between FE predicted and experimentally measured bone strains. This resulted in statically equivalent FE models that explained up to 96% of the variation in experimental strain measurements. Our work serves to guide future in vivo rabbit hindlimb loading studies and enable the use of computational models in the investigation of bone mechanobiology.