Because the ovariectomized rat model of postmenopausal osteoporosis is the most commonly used small animal model to investigate consequences of bone loss on bone structure and strength, or to assess benefits of the various therapeutic strategies to improve bone mass and strength, the attempt was made to compare histoanatomical and structural characteristics of the femoral neck between human and rat models. In addition to different biomechanics, there is a significant difference in gross- and microanatomy of the proximal femur between humans and rats. Percent of the cortical bone component is much higher in rats (72.5%) relative to humans (12.5%). Also, cortical bone at the femoral neck in rats is evenly distributed, whereas in humans there is a considerable difference in the amount of the cortical bone between the superior half of the femoral neck with cortical thickness being only 0.3 mm, and the inferior half of the neck having 6-mm-thick cortex. Humans have far more cancellous bone at the femoral neck (22.7% average) relative to rats (6.8%). In addition, cancellous bone at the femoral neck in humans is unevenly distributed between the bone center and its periphery. Human samples exhibited striking differences in the cancellous bone structure between weight-bearing and tensile trabecular groups exhibiting clear trabecular orientation consisting of plates and rods, and trabeculae around the neutral bone axis with little mechanical activity exhibiting rod-like trabeculae only. Although humans and rats have a periosteum covering the femoral neck, and each lacks the muscular attachment at Intracapsular portions of the femoral neck, rats, in contrast to humans, have the ability to quickly adapt cortical thickness and increase inertia to meet mechanical needs via modeling-dependent periosteal apposition.