Lead is one of the harmful heavy metals that may be produced from human activities, and have deleterious effects on many tissues such as bone. In this research, the effects of oral administration of lead acetate II on histology of rat femur, and expression level of osteocaclcin gene were investigated. Twenty male Wistar rats were randomly divided into 2 groups. The rats in tested group were fed with 100 ppm of lead acetate II during 2 months. The femur samples were removed, fixed and then stained by alizarin red S for mineralization ratio assessment, and Hematoxylin-Eosin for histological studies. Also, real-time PCR was performed to determine the expression level of osteocalcin gene. The dose of 100 ppm of lead acetate II reduced mineralization and bone density, and decreased the relative density of osteoblasts. Also, the diameter of the bone marrow increased while the expression of osteocalcin gene decreased in tested group in comparison with the control group (P < 0.05). The present study suggests that 100 ppm oral doses of lead acetate II might have strong destructive effects on femur histology and osteocalcin expression.