We tested whether β-adrenergic blockade attenuates bone loss and increased marrow adiposity during energy restriction (ER) and whether such an effect is associated with changes in serum leptin and leptin expression in bone and marrow tissues. Female 4-mo-old Sprague-Dawley rats were assigned into four groups (n = 10 each): two groups of 40% ER treated with vehicle (ERVEH; saline) or β-blocker (ERBB; DL-propranolol; 250 μg · kg(-1) · h(-1)) during 12 wk, and two groups of ad libitum-fed controls treated with the same two agents (CONVEH, CONBB, respectively). Over 84 days, CONVEH and CONBB rats gained but ERVEH and ERBB rats lost body fat mass; lean mass did not change in any group. Reduction in serum leptin in ERVEH rats was mitigated in ERBB rats (-5.32 vs. -1.15 ng/ml, respectively). The decline in proximal tibia cancellous vBMD observed in ERVEH rats was attenuated in ERBB rats (-85.24 vs. -53.94 mg/cm(3), respectively). Adipocyte number in ERVEH rats was dramatically higher vs. CON rats at week 12, but this increment was abolished by β-blockade in ERBB animals. The number of osteoblastic cells and marrow adipocytes staining positively for leptin in ERVEH rats tended to be lower vs. that of both CON groups, but β-blockade appears to reverse this effect in ERBB rats. In summary, β-adrenergic blockade mitigated metaphyseal bone loss and bone marrow adiposity during energy restriction and attenuated reductions in serum leptin. These data suggest an important role for β-adrenoreceptor signaling pathway in the cancellous bone and marrow fat response to energy restriction.