Aim To investigate the effects of celastrol on the expression of C-reactive protein and tissue factor in the aorta of ApoE gene knockout mice with earlier atherosclerosis. Methods 8-week old male ApoE gene knockout mice were divided randomly into control group and celastrol treatment group (n=6 in each group). 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). HE staining of root aorta were used to observe the histomorphological change and measure the size of atherosclerotic plaque. The expression of C-reactive protein and tissue factor were detected by immunological histochemical method. Results The area of lipid plaque in the mice treated with celastrol was significantly smaller than that of the control (P<0.05). The value of plaque area/aorta cross section area was also significantly less than that of the control (P<0.05). The expression of C-reactive protein in the aortic wall and tissue factor in the atherosclerotic plaque were significantly lower in celastrol group compared with the DMSO control group (P<0.01 and P<0.05, respectively). Conclusions Celastrol may reduce the formation of atherosclerotic lesions by inhibiting inflammation and promote the stability of atherosc1erotic plaque by reducing the TF production.