Aim To investigate the effects of celastrol on the collagen macrophage migration inhibitory factor and matrix metalloproteinase-9 expressions in the plaque of apoE gene knockout mice gene knockout mice. Methods 8-week old apoE gene knockout mice,male ,were divided randomly into atherosclerosis model group and celastrol treantment group( n=6 in each group). 8-week old male C57BL/6J mice were the normal control. The mice in celastrol group were given. celastrol 2 mg/(kg·d) by intraperitoneal injection for 4 weeks; the mice in control group were only given equivalent amount of dimethyl sulfoxide (DMSO),and the contents of collagen in the aortic atherosclerotic lesions were detected with Picrosirius Red staining. The expression of macrophage migration inhibitory factor and MMP-9 were detected by immunological histochemical method. Results The area of lipid plaque in the mice treated with celastrol was 4270.74±1027.64 μm2 ,significantly smaller than that of the model group 8971.19±1665.76 μm2 (P<0.01). The contents of collagen in the atherosclerotic plaque was significantly higher in Celastrol group compared with model group (mean optical density:0.0275±0.0068 vs 0.0142±0.0054,P<0.01). The expression of matrix metalloproteinase-9 was significantly decreased in celastrol group compared with the model group(mean optical density:0.0054±0.0020 vs 0.0263±0.0080,P<0. 001). The expression of macrophage migration inhibitory factor was also significantly decreased in celastrol group compared with the model tgroup (mean optical density:0.0114±0.0016 vs 0.0227±0.0039,P<0. 001). Conclusions Celastrol can inhibit the progress of atherosclerotic plaque and promote the stability of ather-osc1 erotic plaque in apoE gene knockout mice ,which might be relative to its inhibition on the degradation of collagen and expression of macrophage migration inhibitory factor,matrix metalloproteinase-9 in atherosclerotic plaque of apoE gene knockout mice.