Background: The present study was conducted to evaluate the effect of curcumin as a flavonoid antioxidant on serum lipid profile, oxidative stress, and blood glucose in experimental models of type 2 diabetes (DM2). Methods: Subcutaneous daily injection of dexamethasone (5 mg/kg/day) for a month was performed to induce DM2. For this purpose, 28 adult male Wistar rats were divided into four groups: healthy control group received dexamethasone carrier containing normal saline + ethanol 4% , diabetic control group took 5 mg/kg/day dexamethasone, diabetic group 1 underwent the treatment with 50 mg/kg/day curcumin, and diabetic group 2 underwent treatment with 100 mg/kg/day curcumin. Seven days after dexamethasone injection, curcumin (50 and 100 mg/kg/day) was administrated intraperitoneally for 23 days. At the end of one month, the fasting blood sugar (FBS) level was measured and recorded by glucometer. Later, after a 30-day period, the animals were anesthetized with ether and their blood samples were collected from the heart puncture to measure their serum triglyceride (TG), high density lipoprotein cholrsterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA). Results: The findings showed that curcumin could decrease FBS (P < 0.05), LDL-C (P < 0.01), TG (P < 0.001), and MDA (P < 0.001) and increase HDL-C (P < 0.001) at the end of 30 days. Conclusion: These effects of curcumin can be mediated by increasing either the pancreatic secretion of insulin or releasing from insulin bonds as well as enhancing insulin receptor sensitivity. Moreover, it may prevent the glucose absorption, reduce the activity of 3-hydroxy- 3-methyl glutaryl- CoA reductase (HMG-CoA), or improve the function of liver and pancreas through potent antioxidant properties.