Objective To study the correlation between serum homocysteine ( Hcy ) level and C677T polymorphism of methylenetetrahydrofolate reductase ( MTHFR ) gene C677T polymorphism ( rs1801133) in patients with cerebral infarction, and feature of rs1801133 polymorphism and serum Hcy level in cerebral infarction patients with or without diabetes mellitus.Methods Case-control study.Five hundred and fifty six patients with cerebral infarction admitted to China-Japan Friendship Hospital from January 2014 to January 2015 were included as the case group while 275 subjects from medical examination center without cerebral infarction and diabetes mellitus matched with the case group.MTHFR C677T polymorphism was determined by pyrosequencing and serum Hcy was determined by circulating enzymatic.Chi-square test was used to analyze the distribution of genotype in different group; ANVOA was used to analyze the Hcy level with different genotype in patients with cerebral infarction, and LSD-t was used to pairwise comparison.Results Among the 556 patients with cerebral infarction ,TT genotype were 202 cases (36.33%), CT genotype were 257 cases(46.22%), CC genotype were 97 cases(17.45%).The T allele 44%, higher than the control group T allele frequencies 46.91%(χ2 =23.385,P<0.001).The level of TT genotype serum Hcy level (21.31 ±17.31) μmol/L were higher than CT genotype (14.88 ±7.71) μmol/L(P<0.001)and CC genotype(14.48 ±7.78) μmol/L(P<0.001).There is no significant statistics different in TT genotype frequency between Cerebral infarction patients with diabetes mellitus(36.77%) and without diabetes mellitus(36.44%) (χ2 =0.031,P>0.05), while the level of serum Hcy in Cerebral infarction patients with diabetes mellitus ( 18.16 ±12.90 )μmol/L is lower than Cerebral infarction patients without diabetes mellitus(23.47 ±19.53) μmol/L in TT genotype( F=4.652, P<0.05).Conclusions MTHFR TT genotype was related to serum hyperhomocysteine, and maybe save as the risk of cerebral infarction.The Hcy level in TT genotype cerebral infarction patients with DM is lower than the same genotype patients without DM.(Chin J Lab Med, 2016, 39:205-209 )