Aim To investigate the effect of overexpression of omentin on collagen content in aorta of diabetic atherosclerosis rats. Methods 60 one-month-old male Wistar rats were randomly divided into normal control group (NC group; n＝8) and experimental group (n＝52). The experimental group was fed with high-fat and high-sugar diet and injected 2% streptozotocin (30 mg/kg) into tail vein to establish diabetic rat model. The diabetic rats were fed with vitamin D3 (0,0 IU/kg) for 16 weeks to establish a diabetic rat model with arteriosclerosis. 24 diabetic atherosclerosis rats were randomly divided into diabetic atherosclerosis group (DAC group; n＝8), diabetic atherosclerosis plus empty virus group (DAC＋E group; n＝8) and diabetic atherosclerosis plus omenin group (DAC＋O group; n＝8). 150 μL adeno-associated virus carrying human omentin gene ITLN1-AAV9 and 150 μL virus carrying empty plasmid were injected into DAC＋O group and DAC＋E group via tail vein, respectively, and equivalent physiological saline was injected into NC group and DAC group. The rats were fed with high-fat diet for 4 weeks. The serum and liver omentin and blood lipid levels were measured. The aorta was taken for HE staining. Quantitative real-time polymerase chain reaction was used to determine the contents of collagen Ⅰ, Ⅲ, matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA. Protein contents of collagen Ⅰ, Ⅲ, MMP-2 and MMP-9 in aorta were determined by Western blot. The content of aortic superoxide dismutase (SOD) was determined by xanthine oxidase method. Aortic malondialdehyde (MDA) levels were measured by thiobarbituric acid condensation method. Results (1)Compared with NC group, the level of serum omentin in diabetic atherosclerosis rats decreased significantly. After intravenous injection of adeno-associated virus carrying human omentin gene, in DAC＋O group, the serum and liver levels of human omentin were 101.0±0.2 and 98.3±1.9 μg/L, respectively. Human omentin was not detected in corresponding tissues of other groups. (2)Compared with DAC group, serum lipid profile and aortic MDA in DAC＋E group and DAC＋O group decreased significantly, while SOD increased, but there was no significant difference between the latter two groups. (3)In DAC group, aortic intima was partially exfoliated, smooth muscle was proliferated, local hyalinization and calcification were observed. In DAC＋O group, the intima was intact, the local wall was thickened, the degree of smooth muscle proliferation and calcification was significantly improved compared with DAC group. (4)Compared with DAC＋E group, the expressions of collagen Ⅰ and Ⅲ mRNA and collagen Ⅲ protein in DAC＋O group decreased significantly. Compared with DAC＋E group, there was no significant difference in the expressions of MMP-2, MMP-9 mRNA and protein in DAC＋O group. Conclusion In diabetic atherosclerosis rats, overexpression of human omentin can reduce the expression of collagen Ⅲ in aorta, alleviate atherosclerosis, and has no significant effect on oxidative stress level.