Abstract: Objective: To observe and compare the effect of cyanocobalamin and methylcobalamin（methyl-B₁₂） on renal disease of type 2 diabetic Kkay mice with hyperhomocysteimia induced by high methione food. Methods: Type 2 diabetic Kkay mice were fed with 3% methionine high fat diet until the level of serum homocysteine increased to 15 μmol/L.Then,the mice were randomly divided into control group,cyanocobalamin and methylcobalamin groups,respectively.Serum homocysteine was measured at weeks 0,1,2,4,8,and 24h urine was collected for detecting urine albumin and creatinine. Results: The level of homocysteine was progressively increased in control group,and decreased after treatment with cyanocobalamin and methylcobalamin.The UAE and urine NAG activity in all groups were increased without use of hypoglycemic agents,but the increased amplitude was lower than that in the other two groups. Conclusion: Both cyanocobalamin and methylcobalamin can effectively decrease the level of total homocysteine in type 2 diabetic mice with hyperhomocysteinemia,and delay the progression of renal disease of type 2 diabetic mice.