Aim: According to World Health Organization data, around 1.5 billion people in the world use tobacco products. Nicotine, the most common use of tobacco, is the main psychoactive substance that causes addiction. Exposure to nicotine during pregnancy increases the risk of low placenta weight, stillbirth, congenital heart disease, musculoskeletal defect. Antioxidants are used to protect against teratogenic substances such as nicotine. The purpose of the study was to determine the skeletal system malformations caused by low (3 mg/kg) and high (6 mg/kg) doses of nicotine during embryonic bone evolution by using the double skeletal staining method and the protector role of vitamin E in preventing these malformations.Material and Method: The rats were divided into 6 groups: the control, low-dose nicotine, high-dose nicotine, low-dose nicotine+vitamin E, high-dose nicotine+vitamin E and vitamin E. The development of the skeletal system of the fetuses was examined by the skeleton staining method. The anterior and posterior extremity images of the fetuses were examined under the stereomicroscope and then through photographing total bone length, ossification length and ossification rate were calculated in the ImageJ program. Results: There was an important decline in the total bone length, ossification length and ossification rate (p<0.05) in the bone measurements of the front and hind extremities, while it was found that the treatment groups approached the control group and the increases were important (p<0.05). Conclusion: It was concluded that being to nicotine during pregnancy delayed skeletal ossification and that vitamin E, which is an antioxidant, may be protective opposite the teratogenic effect of nicotine on the bone.