Simvastatin is a hypolipidemic drug which is used to control hypercholesterolemia and to prevent cardiovascular disease. In the current study, the effects of high and low doses of simvastatin treatment on tibia of healthy rats were investigated. Wistar rats were used for the control, 20 mg and 50 mg simvastatin-treated groups. Molecular investigations were performed using Fourier transform infrared spectroscopy. In the bones of the two groups of simvastatin-treated rats, the relative mineral/matrix ratio (p < 0.001), relative carbonate content (p < 0.001), carbonate/amide I ratio (p < 0.001) and crystallinity (p < 0.001) decreased significantly compared to the control group. Low dose of simvastatin treatment is more effective in reducing the relative carbonate content indicating the amount of carbonate substitution for phosphate in the mineral crystal. The olefinic band almost disappeared in the high dose of simvastatin-treated group which implies a decrease in unsaturation and an increase in lipid peroxidation. The higher frequency value and the bandwidth of CH2 asymmetric stretching band for the 50 mg treated group imply more disordered (p < 0.001) and fluid (p < 0.001) membrane structure. Low dose of simvastatin is more effective in strengthening the bone than high dose simvastatin treatment. High dose simvastatin treatment induces lipid peroxidation and changes the lipid composition and concentration, which are known to affect membrane physical properties. (C) 2010 Elsevier B.V. All rights reserved.