OBJECTIVE： To investigate the effects of glimepiride combined with metformin on glucose and lipid metabolism， islet function and serum miR-126 expression of newly diagnosed type 2 diabetes patients. METHODS： A total of 100 patients with newly diagnosed type 2 diabetes in Nanchuan Hongren Hospital of Chongqing during Jan. 2014-Jan. 2017 were divided into observation group and control group according to random numble table， with 50 cases in each group. Control group was given Metformin hydrochloride sustained-release tablets （Ⅱ） with initial dose of 0.5 g， once a day， adjusted to 0.5 g 12 weeks later， twice a day， maximal dose of 1 g at meal or after meal. Observation group was additionally given Glimepiride tablets 2 mg， once a day， at breakfast， on the basis of control group. Both group were treated at lasted for 24 weeks. The levels of blood glucose （FPG， 2 hPG， HbA1c）， blood lipid （TC， TG）， islet function （FINS， 2 hINS， FCP， 2 hCP， HOMA-IR）， serum miR-126 before and after treatment and the occurrence of ADR were observed in 2 groups. RESULTS： Before treatment， there was no statistical significance in the levels of blood glucose， blood lipid， islet function or serum miR-126 expression between 2 groups （P＞0.05）. After treatment， the levels of blood glucose， blood lipid and HOMA-IR in 2 groups were significantly lower than before treatment， and the levels of blood glucose and HOMA-IR in observation group were significantly lower than control group. The levels of FINS， 2 hINS， FCP and 2 hCP， serum miR-126 expression in 2 groups were significantly higher than before treatment， and the observation group was significantly higher than control group， with statistical significance（P＜0.05）. No obvious ADR was found in 2 groups during treatment. CONCLUSIONS： Glimepiride combined with metformin can significantly improve glucose and lipid metabolism， islet function， and regulate serum miR-126 expression without increasing the occurrence of ADR.