Abstract: Objective To explore the effects of excessive lead (Pb) on bone metabolism,and its mechanism.Methods Forty specific pathogen free (SPF) male Sprague-Dawley (SD) rats aged 21 days with adaptive feeding of 7 days were randomly divided into 4 groups:a normal control group (with distilled water),low,medium,and high Pb group (with water containing 0.1%,0.2%,and 0.3% CH₃COO₂ lead).By the end of 60 days' treatment,the rats were weighed;the contents of Pb,calcium (Ca) in bone tissues were determined with inductively coupled plasma (ICP) method.The rat bone morphology was examined via conventional hematoxylin-eosin staining.The expression levels of wingless-type mouse mammary tumor virus integration site family member 2 (Wnt2),transcription factor 1 (Tcf-1),peroxisome proliferator-activated receptor γ (PPAR-γ) and β-catenin gene were determined with real-time reverse transcriptase PCR(RT-PCR).Results Compared with those of the normal control group,the bone lead concentration in lead overload groups increased (0.221 5±0.033 0,0.335 3±0.040 7,and 0.399 2±0.030 9 mg/g),while the calcium content decreased (21.719 4±1.120 8,21.559 5±1.094 0,and 21.421 7±0.700 2 mg/g)significantly with the increment of lead exposure (all P<0.05).Compared with the normal control group,the low and medium lead exposure group showed attenuated trabecular of femur and the high lead exposure group showed decreased,attenuated,and broken trabecular of femur and expanded bone marrow cavity.Compared with those of the normal control group,the expression level of PPAR-γ (0.821 3±0.020 2),Wnt2 (0.852 6±0.030 8),Tcf-1 (0.8743±0.077 2),and β-catenin gene (0.874 5±0.055 3)in the high lead exposure group decreased significantly(all P<0.05).Conclusion Lead could inhibit the absorption of Ca in bone tissue and could damage bone structure in rats and the mechanism of the effect may be related to down-regulations of ppar-γ,Wnt2,Tcf-1,and β-catenin associated gene expression in bone tissue.