An experiment was designed to investigate whether systemic administration of tetracyclines (TCs) as bone fluorochrome labels could interfere with bone modeling in vivo and inhibit osteoclast formation and activity in vitro. Cell cultures of rat bone marrow macrophages revealed that TC and oxytetracycline inhibited osteoclastogenesis and bone resorption and stimulated apoptosis. Forty rats in five groups were treated with saline, calcein green, alizarin red S, TC, or oxytetracycline. Their tibias were used for histomorphometric analysis, including bone static, dynamic, and resorption parameters in the tibial proximal metaphysis. No significant differences in bone volume per tissue volume, trabecular number, trabecular thickness, trabecular separation, bone formation rate per bone surface, mineralizing surface, or mineral apposition rate were observed. TC or oxytetracycline decreased eroded surface, number of osteoclasts per bone perimeter, and osteoclast surface per bone surface by about 50%. The results demonstrated that TC and oxytetracycline inhibit rat osteoclast formation and activity in vitro, and histomorphometric parameters involved in bone turnover may be affected by the use of oxytetracycline and TC as fluorescent bone labels in vivo.