Objective The purpose of this study was to explore the effects of composition of Ophiopogon polysaccharide， Notoginseng total saponins and Rhizoma Coptidis alkaloids（CONR） on Oxidative stress reaction of diabetic atherosclerotic rabbit modle by interventing AGEs/p38 mitogen-acti-vatedproteinkinase（p38MAPK） signal pathway. Methods Setting up blank group， model group， CONR high-dose group， CONR low-dose group， SB203580 group， simvastatin group. DA rabbits were established by alloxan intravenous injection with abdominal aorta intima balloon injury， the experimental groups were daily given CONR 450 mg/kg and CONR 150 mg/kg， Simvastatin 3mg/kg for 10 weeks， SB203580（p38MAPK inhibitor） 2 mg/kg intraperitoneal injection， 12 h repeated for 10 weeks； in the control group， 20 mL of saline was daily administered. Rusults The serum AGEs of the model group were higher than that in the blank group， and the difference was statistically significant（P<0.01）. After 10weeks of administration， the experimental groups had reduced effect on AGEs， which was statistically significant compared with the model group. The high expression of p-p38mapk protein in each group were inhibited significantly compared with the model group（P<0.01）. The inhibitory effect of p-p38MAPK protein in CONR high and low dose group， simvastatin group were better than that in SB203580 group（P<0.01）. There was no statistically significant difference between CONR high and low dose group and simvastatin group（P<0.01）， there was statistically significant difference compared with normal control group（P<0.01）. The MDA in model group were higher than that in blank group. After the treatment， CONR high dose group， the SB203580 group and simvastatin group has lower effect on MDA in DA big rabbit（P<0.01）； The SOD activity was significantly enhanced in the experimental groups（P<0.01）. Conclution The traditional Chinese medicine composition may be able to inhibit Oxidative stress reaction of atherosclerotic rabbit modle by interventing p38MAPK signal pathway.