Aim To observe the effects of treatment with celecoxib, a specific cyclooxygenase-2 inhibitor, together with low-dose aspirin on atherosclerosis progression in an apolipoprotein-E knockout (ApoE -/-) mice model. Methods 8-week-old ApoE -/- mice fed on a western-diet were devided into group aspirin (n=10), group aspirin+celecoxib (n=11), and group placebo (n=8). Aspirin, aspirin+celecoxib and placebo were given respectively by oral gavage. Wildtype mice fed on a normal diet were as normal control group (n=6).At 16 weeks of age, serum total cholesterol (TC) and triglyceride (TG) were determined, atherosclerotic lesions in arotic root were evaluated by oil red O staining. Results A small difference in serum TC and TG levels was found either in group aspirin or in group aspirin+celecoxib compared with group placebo (30.2±5.5 mmol/L and 28.6±6.2 mmol/L vs 37.8±8.1 mmol/L,p<0.05, p<0.05); However, there was no significant difference between the two treatment groups. Oil red O staining showed that mean plaque size in arotic root was significant smaller either in group aspirin+celecoxib or in group aspirin compared with group placebo (p<0.01), and it was much smaller in group aspirin+celecoxib (0.042±0.026 mm2 vs 0.068±0.022 mm2, p<0.05). Conclusions Aspirin can slightly decrease serum level of TC in ApoE -/- mice; Celecoxib, together with low dose aspirin, can reduce the progression of atherosclerosis to a much more extent