Background:The prevalence of Type 2 diabetes mellitus and its associated micro and macro-vascular complications are globally rapidly increasing. Studies show that most diabetic complications are associated with an inflammatory response. YKL- 40, a novel biomarker for acute and chronic inflammation, has been proved to have a role in these complications. Many classes of antidiabetic drugs may have modulatory effects on inflammation beyond their glucose‐lowering activity. So, inThis study we evaluate comparative effects of metformin and glimepiride on ykl-40 serum level in type2 diabetic patients. Patients and method(s):In a parallel-group, randomized trial setting, 46 newly diagnosed, medication-naïve type 2 diabetes patients were assigned to metformin (in divided doses, 500 -850 mg tablets three times daily) (n = 23) or glimepiride (1-4 mg once daily) (n = 23). Serum concentrations of YKL-40, along with HbA1c were measured at baseline visit and after 4 months. Result(s): Both drugs were equally effective to achieve glycemic control. However, metformin caused more significant reduction in YKL-40 concentrations after 4 months when compared to glimepiride (P < 0.05). Conclusion: /From the present study it is hypothesized that metformin is more effective than glimepiride in reduction of YKL-40 level (inflammatory diabetic complications).