Aim To investigate the changes of autophagy of the common carotid atherosclerosis (As) at the different stages in apolipoprotein E gene knockout (ApoE－/－) mice. Methods 6-weeks-old male ApoE－/－ mice (n=40) were randomly divided into two groups and fed with common adaptability diet for 2 weeks. The mice of the control group (n=10) received a sham operation and the common diet for another 8 weeks. While the model mice (n=30) received a right common carotid artery cannulation and then were randomly subdivided into three groups (the 2 weeks, the 4 weeks and the 8weeks) and fed with the high fat diet separately for 2 weeks, 4 weeks and 8 weeks. The blood samples obtained from femoral arteries were studied via the biochemical analysis. The right common carotid arteries were split out for TEM and histopathological study. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the relative expression levels of mRNA and protein about ATG5, Beclin1 and LC3-Ⅱ. Results As the operation time prolonged the lipid levels especially TG and LDLC were increased time-dependently. The histopathological analysis results showed that there was a small amount of cells infiltrated in the common carotid artery in the 2 weeks, although the wall was still unspoiled. The vascular wall in the 4 weeks was messy and there was thrombus in the vascular lumen. The thickness of the right common carotid artery in the 8 weeks was higher than the rest and its elastic membranes significantly decreased. The TEM study indicated that the quantity of autophagosomes in the 4 weeks was higher than other groups and its lipid droplets was still higher than the 2 weeks but lower than the 8 weeks. The qRT-PCR and Western blot detection suggested the mRNA and protein expression of ATG5, Beclin1 and LC3-Ⅱ in the 4 weeks was higher than the 2 weeks and the 8 weeks, and the expression in the 8 weeks was also higher than those in the 2 weeks. Conclusion Autophagy was continuously stimulated during As formation, however, the levels of autophagy will decrease after reaching the peak at a time.