Diabetes is associated with low bone formation. In this study we investigate the effect of additional or reduced mechanical loading on indices of bone formation and resorption, bone mass, and biomechanical properties in spontaneously diabetic BB rats. Female diabetic (mean age 13 weeks) and age-matched control rats were each allocated to three experimental groups: no-intervention; supervised running exercise program (Ex); and unloading induced by unilateral sciatic neurectomy (USN). The study period was 8 weeks. We measured biochemical parameters of bone formation (plasma osteocalcin) and resorption (urinary deoxypyridinoline [Dpd]); bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at middiaphyseal and metaphyseal regions of the femur; histomorphometry of the proximal tibial metaphysis (PTM); and biomechanical properties of the femur (neck, diaphysis, and metaphysis) and lumbar vertebra (L-5). In nondiabetic rats, Ex did not affect parameters of bone formation/resorption and BMD, and had little effect on biomechanical properties. USN increased Dpd excretion, whereas there was a decreased trabecular bone formation rate (BFR) on morphometry of PTM in both paralyzed and intact limbs. Compared with intact limbs, paralyzed limbs of USN rats showed decreased trabecular bone volume at the PTM, and decreased BMD and biomechanical properties at the distal femoral metaphysis (DFM) and, to a lesser extent, femoral neck. Diabetic rats of the three experimental groups had low plasma osteocalcin levels and Dpd excretion, as well as low BFR on morphometry. The BMD and biomechanical properties of both femur and L-5 were unchanged in diabetic rats. Diabetic Ex rats, however, showed a lower maximum load and stress at DFM than control Ex rats. Diabetic USN rats showed no increase in Dpd excretion; their paralyzed limbs showed decreased maximum load at DFM, but there was no significant decrease in trabecular bone volume at PTM or BMD at DFM. Thus, the running exercise does not affect low bone formation in diabetic rats; however, trabecular bone loss caused by disuse is less pronounced in diabetic rats, probably as a result of low bone resorption.