Diabetic patients have a markedly increased risk of cardiovascular disease compared with non-diabetics. Two drug groups today target insulin resistance; biguanides and thiazolidinediones. In addition, these may have other effects on cardiovascular risk factors. The aim of this study was to evaluate the effects of metformin and rosiglitazone on non-traditional cardiovascular risk factors. Forty type 2 diabetic patients were randomized into metformin and rosiglitazone groups. After receiving the optimal doses, the patients were monitored for 12 weeks. Biochemical parameters, lipid parameters, CRP, insulin, c-peptide, and HbA1c levels were analyzed. VWF, PAI-1, ICAM-1, TNF-alpha, IL-6, E-selectin, and fibrinogen levels were measured in order to assess coagulation status and endothelial dysfunction. In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-alpha levels were significantly decreased after 12 weeks compared with the basal levels. IL-6 levels decreased from 75 pg/ml +/- A 20 to 42 pg/ml +/- A 9 (P 0.023) and TNF- alpha levels from 61 pg/ml +/- A 31 to 39 pg/ml +/- A 10 (P 0.018). In the rosiglitazone group, FPG, PPG, HbA1c, insulin, HOMA-IR, IL-6, and TNF-alpha levels decreased significantly after 12 weeks compared with the basal levels. IL-6 levels decreased from 78 pg/ml +/- A 21 to 41 pg/ml +/- A 9 (P 0.028) and TNF-alpha levels from 62 pg/ml +/- A 19 to 37 pg/ml +/- A 10 (P 0.012). At the end of the study, no significant differences were determined between groups. Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation. Both metformin and rosiglitazone were effective in controlling inflammatory markers in addition to metabolic parameters.