Methylenetetrahydrofolate reductase (MTHFR) polymorphism may play an important role in the pathophysiology of obesity and diabetes accompanied by obesity due to its influence on plasma homocysteine levels. There are significant and sometimes very strong relationship between levels of homocysteine and several multi-system diseases including CHD and CVA. To examine the association between MTHFR gene C677T polymorphism in diabetes and obesity with serum homocysteine levels. A total of 682 subjects were recruited in four groups (Normal, obese, diabetic and obese and diabetics). MTHFR gene C677T polymorphism was detected using PCR-RFLP technique. Serum homocysteine levels were measured using HPLC. There was a significant increase in the mean serum homocysteine levels in subjects carrying TT genotype (34.6 +/- 26.5) compared to subjects carrying CC (15.1 +/- 8) or CT genotype (16.4 +/- 7.8) (P < 0.000). We found no significant differences for MTHFR allele and genotype frequencies between different groups. Our data have confirmed the association between serum homocysteine levels and MTHFR C677T genotype reported in other populations.