Musculoskeletal disorders affect hundreds of millions of people around the world today and remain a major threat especially to women and the elderly. It is clinically important to understand how the musculoskeletal system adapts to its physiological environments and remains healthy. This thesis includes four studies that investigate the role of bone interstitial fluid flow in bone adaptation and metabolism. The first study investigated how the different sized bone pores affect interstitial fluid flow in mechanically loaded bone. I developed a theoretical model and predicted the non-linear cusp-like fluid pressure profiles around the osteonal canals, which had been found experimentally but previously unexplained. The second study addressed the paradox that net solute transport occurs in cyclically loaded bone when the net fluid transport is zero. A lacunar-mixing process was proposed that for the first time outlined a detailed mechanism of convective mass transport from the blood supply to the osteocytes. The convective transport was found to increase with increasing loading amplitude and decrease with increasing loading frequency. The third study involved in vivo tracer experiments to quantify the tracer movement in the absence of mechanical loading and to delineate the bone interstitial fluid pathway Four tracers of various sizes (reactive red. microperoxidase (MP). horseradish peroxidase (HRP). and ferritin with a molecular diameter o f approximately 1, 2, 6, and 10 nm, respectively) were injected into the rat circulation. The number of the osteocytes labeled with these tracers was found to decrease with increasing molecular size. Results from this study suggest that the pore size o f the interstitial fluid pathway is between 6-10 nm, because reactive red, MP, and HRP appeared in osteocytic lacunae while ferritin was found only in vascular pores. Finally, in the fourth study the osteogenesis of the blood pressure induced interstitial fluid flow were examined under the condition of venous stasis. The model showed that the shear stress on osteocytic membrane due to blood flow is too small to account for the periosteal bone growth associated with venous stasis. I postulated that the elevated pressure on the periosteum might trigger the periosteal response in venous stasis.