Abstract： Objective To investigate the effects of ISO-1, a selective macrophnge migration inhibitory factor(MIF) tautomerase activity inhibitor,on the growth and anginogenesis of colorectal cancer in mouse modal, and to explore its probable mechanism. Methods CT26 cells were treated with various concentrations of ISO-1 (0.01-100 umol/L) for 24,48 and 72 hours. MTr assay was used for detecting the inhibition effect of ISO-1 on CT26 cell proliferation. The method of orthotopic transplantation,with fresh tumor masses planted into the hernial sac of cecum by operation, was used to establish mouse model of colorectal cancer. Thirty mice were divided into three groups randomly and treated with ISO-1 (0.2 ml,20 mg/kg), 5% DMSO and NS (normal sodium) twice a week intraperitoneally. Tumor volumes were measured twice a week.After 4 weeks, the mice were sacrificed and serum VEGF concentratious were tested using ELISA.Immunohistochemical staining of CD31 was used for comparing microvessel density (MVD)of tumor tissues.Results In vitro,ISO-1 significantly inhibited CT26 cell proliferation. Also ISO-1 significantly reduced the tumor volumes in vivo. The inhibition ratio of tumorvolume was 25.22% and 9.65% after 4 weeks in ISO-1 and DMSO group, respectively (P<0.01). Compared with DMSO treatment, ISO-1 reduced the tumor weights [(1.50±0.14) g vs (1.80±0.14 ) g, P=0.017]; and decreased VEGF levels and MVD of tumor tissues significantly [VEGF: (14.62±6.49) ng/L vs (63.34±10.22) ng/L,P<0.01; MVD: 16.6±3.7vs 35.8±7.3,P=0.002]. Conclusions ISO-1 inhibits CT26 cell proliferation and tumor growth. The probable mechanism may be associated with the inhibition of MIF biological activities, down-regulation of the expression of VEGF and reduction of MVD.