Abstract: Objective To investigate the effect and mechanism of oxaliplatin on colon cancer in rats. Methods Forty-two SD rats were subcutaneous injected with dimethylhydrazine, once a week, continuously for 5w. The establishment of colon cancer model was determined by pathological observation through rectum HE staining of 2 rats randomly. The rest of 40 colon cancer rats were randomly divided into the following four groups containing 10 rats per group: model group, oxaliplatin high-dose, medium-dose and low-dose groups. Normal group contained 10 SD rats. The 1 ml 5% glucose injection solutions of oxaliplatin were injected into the rats tail vein in oxaliplatin groups(27.2, 13.6, 6.8 mg/kg), once every three weeks, continuously for 12 w. Normal group and model group were injected with 1 ml 5% glucose injection. The rats were sacrificed by cervical dislocation 48 hours after the last administration. The number of colon tissue mutation crypt foci (ACF) was observed by microscope. ELISA was used to detect the change of serum CD44v6 and VEGF levels. Caspases-3, Caspases-7 and survivin expression were assessed by Western blot. Results Compared with the model group, the number of ACF in colonic tissues in oxaliplatin treatment groups was significantly reduced. Compared with normal group, the serum CD44V and VEGF levels in model group were significantly increased(P＜0.05). While compared with the model group, the serum contents of CD44V and VEGF in oxaliplatin high-dose and medium-dose groups were decreased, especially oxaliplatin high-dose group showed better effect on that, and the difference was statistically significant(P＜0.05). Compared with normal group, the expression of survivin, Caspase-3 and Caspases-7 proteins in colonic tissues were up-regulated in the rats of model group and oxaliplatin groups. Compared with model group, the protein expression of survivin were reduced by oxaliplatin treatment, meanwhile, the expression of Caspases-3, Caspases-7 protein were enhanced significantly (P<0.05). Conclusion The effect of oxaliplatin on colon cancer is associated with ameliorating the carcinoma angiogenesis and metastasis, inhibiting cell apoptosis in colon tissues through regulating the levels of CD44V6, VEGF, survivin, Caspase-3 and Caspase-7.