OBJECTIVE To investigate the effects of centipede acidic protein (CAP) on atherosclerotic rats and the mechanisms involved. METHODS Male Sprague-Dawley rats were randomly divided into five groups: control, atherosclerotic, low-dose CAP (L-CAP), high-dose CAP (H-CAP) and simvastatin group (n=12 in each group). Atherosclerotic model was established by a single dose of vitamin D(3) and an atherogenic diet. Rats of H-CAP and simvastatin groups simultaneously received CAP or simvastatin daily for 6 weeks. At the completion of the experiment, the changes in lipid profile, hemorrheology, nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA) and superoxide desmutase (SOD) were measured, and the histological changes in aorta and liver were observed. RESULTS Treatment of atherosclerotic rats with either low or high doses of CAP led not only to significant decreases in plasma total cholesterol, triglyceride, low density lipoprotein and increase in plasma high density lipoprotein, but also to improvement of the hemorrheologic abnormalities. On the other hand, CAP suppressed the lipid peroxidation, regulated the levels of ET-1 and NO. From the histopathological examination, treatment with CAP ameliorated the pathological changes in thoracic aorta and liver in atherosclerotic rats. CONCLUSIONS These results suggest that CAP significantly suppress the development of atherosclerosis, improves the hemorrheological disturbances and histopathological changes in the atherogenic diet fed rat model. These effects may partly attribute to reverse of dyslipidemia, inhibition of lipid peroxidation, regulation of NO and ET-1 system.