Aim To investigate the RELMɑ/FIZZ1 signal pathway in intervening atherosclerosis in experimental animals, and inspect its influences on angiogenesis. Methods 20 ApoE^－/－ mouse were fed with high fat diet for 12 weeks and randomly divided into 2 groups equally. The model group were fed with high fat diet and another group were fed with high-fat diet but were injected with RELMɑ/FIZZ1 for 2 weeks. 10 C57BL/6J mice were fed with normal diet for control The positive area of plaque were determined. The RELMɑ/FIZZ1 and CD34 positive response intensity at aorta vessel wall, and the capillary density in plaque were measured by immunohistochemical staining. Investigate the abnormally expressed genes and changed signal pathway via array hybridization. Results Compared to control group, model group atherosclerosis plaque formed in mouse arteriae. RELMɑ/FIZZ1 protein had obvious expression by immunohistochemistry in atherosclerotic plaque. Compared to model group, the correcting plaque area was significantly increased in RELMɑ/FIZZ1 group （31.58%±6.65% vs 24.16%±3.59%, P<0.01）. The RELMɑ/FIZZ1 and CD34 positive response intensity and the capillary density in RELMɑ/FIZZ1 group were higher than those in model group （P<0.01）. Array hybridization data analysis shows that 856 genes expressed difference significantly, which 391 genes raised while 465 genes lowered, and 22 signaling pathways are significantly different, including that 12 signaling pathways are activity raised while 10 signaling pathways are activity down. Conclusions RELMɑ/FIZZ1 could promote the progression of atherosclerosis plaque by stimulating angiogenesis. The mechanism has a close relationship with the significant expression of Atg9a and Gng8 genes, the regulation of actin cytoskeleton pathway （rno04810） and the activation of gap junction （rno04540） cell.