Objective: To evaluate the feasibility of 99 Tc m -3PEG4-RGD targeted to micro-vessels for detecting vulnerable plaque on rabbits with SPECT/CT imaging. Methods: A total of 15 male New Zealand white rabbits were randomly divided into normal diet group (group A, n=5), vulnerable plaque group (group B, n=5) and stable plaque group (group C, n=5). The animals were given sham operation separating femoral artery (group A, C) or abdominal aorta balloon injury (group B) 2 weeks after feeding. 99 Tc m -3PEG4-RGD was injected at the end of the 4, 8 and 12 week. SPECT/CT images were captured 0.5, 1 and 2 h after injection. One rabbit was executed at the end of the 4 and 8 week, and the rest were executed at the end of the 12 week in each group, and then vitro SPECT imaging, pathology and immunohistochemistry analysis were performed. Results: At the end of the 4 week, no uptake in aorta was observed in all 3 groups, and the difference of target/non-target ratio (T/NT) was not significant among 3 groups 0.5 h after injection (F=2.515, P=0.122). At the end of the 8 week, there was certain radioactive uptake in group B and group C (F=17.037, P=0.001). At the end of the 12 week, the uptake in group B was much higher than that in group A and group C (F=43.710, P<0.001). The amount of micro-vessels in group B was significantly higher than that in group C. Histopathology results showed that at the end of the 12 week, AHA atherosclerotic type of rabbits in group B was type III and IV, while was type II in group C. There was no vulnerable plaque nor micro-vessels in rabbits of group A. Conclusion: 99 Tc m -3PEG4-RGD has certain value for noninvasively evaluating the stability of arterial plaque in rabbits. Copyright © 2014 by the Press of Chinese Journal of Medical Imaging and Technology.