Although cadmium (Cd) and fluoride may both have adverse effects on bone, most studies focus on a single agent. In this study, we investigated the effects of cadmium and fluoride on bone at a relative low level. Sprague-Dawley male rats were assigned randomly into four groups which were given sodium chloride, cadmium (50mg/L), and fluoride (20mg/L) alone, or in combination via drinking water. At the 12th week, urine, blood, and bone tissues were collected for biomarker assay, biomechanical assay, and histological assay. Cadmium had significantly adverse effects on bone mineral density, bone biomechanical property, and bone microstructure. Fluoride slightly increased vertebral bone mineral density but negatively affected bone biomechanical property and bone microstructure. Fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium but could not improve the damage of bone biomechanical property and microstructure caused by cadmium. Tartrate-resistant acid phosphatase 5b levels in rats treated with cadmium and fluoride or in combination were 1-2.5 folds higher than the control. Our data suggest that low level of fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium exposure but has no influence on appendicular skeleton damage caused by cadmium.