The effects of nandrolone decanoate (ND) treatment on bone mass and metabolism were studied in ovariectomized (OVX) rats with osteopenia. The 6-month-old rats were divided into Sham (n = 12) and OVX (n = 24). The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post ovariectomy, the OVX rats were divided into two groups: (1) OVX + Vehicle and (2) OVX + ND. The effects of ND on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism were studied by dual-energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. After 24 weeks of treatment, histomorphometry of the right tibiae and the wet weight of the gastrocnemius and soleus skeletal muscles were also examined. Ovariectomy resulted in a significant increase in biochemical markers and a significant decrease in spine BMD (0.221 ± 0.016 g/cm2 in OVX group vs 0.239 ± 0.008 g/cm2 in Sham group) and BMC (0.550 ± 0.055 g in OVX group vs 0.605 ± 0.042 g in Sham group) at 6 weeks post ovariectomy. Spine BMD (0.227 ± 0.017 g/cm2), femoral BMD (0.263 ± 0.012 g/cm2), and bone density of femur (1.035 ± 0.036 g/cm3) in the OVX + ND group were significantly greater than those in the OVX + Vehicle group (0.204 ± 0.013 g/cm2 for spine BMD, 0.243 ± 0.009 g/cm2 for femoral BMD, 0.938 ± 0.06 g/cm3 for bone density of femur) after 24 weeks of treatment. ND treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Histomorphometric findings indicated that ND-treated rats had greater cancellous bone volume, greater trabecular number, greater trabecular thickness, and less trabecular separation than vehicle-treated OVX rats. OVX rats had greater wet weight of the gastrocnemius and soleus muscles than rats treated with ND. The data suggest that the effect of ND on bone mass is not influenced by the condition of the muscles in OVX rats. Our findings indicate that ND blocks further bone loss by inhibition of bone resorption in OVX rats with osteopenia.