Abstract: Objective: Prosthechea michuacana is a Orchidaceae used as anti-inflammatory, to depurate the circulatory system, treat renal disease and diabetes. The aim of present study was to investigate the effect of two new triterpenes isolated from hexane extract from bulbs of Prosthechea michuacana in streptozotocin plus nicotinamide-induced type 2 diabetic mice. Method: Tetracyclic triterpenoids have been isolated from the bulbs hexane extract from P. michuacana which were identified by spectroscopic analysis to be 24-methyl, 24-hydroxy-5α-lanosta-9 (11), 25-dien-3α-acetate (1) and 24-methyl-24-hydroxy-5-lanosta 9(11)-en-3α acetate (2). Streptozotocin-nicotinamide-induced mildly diabetic mice was established to investigate the antidiabetic activities. The present study evaluated the effect of hypoglycaemic, hypolipidemic, oxidative stress, insulin resistance, of the triterpenoid 1 and 2 from P. michuacana. Diabetic mice were treated with 1 and 2 for a 30 days period and a set of biochemical parameters were studied including: Glucose level, total cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, effect on RIN-5F cells from AGEs-induced oxidative stress and TNF-α and IL-6 levels in serum. We also looked into liver function by determining glucose-6-phosphatase, glucokinase and hexokinase activities and the effect on insulin level. Results: Both triterpenes significantly reduced the intake of food, water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein and increase HDL-cholesterol. The treatment improves TBARS-reactive substance level and SOD, CAT, GSH and GPX. The administration of 20 mg kg-1 exhibited a significant increase in serum and pancreas tissue insulin. The triterpenes decreased serum glucose in streptozotocin-nicotinamide-induced mildly diabetic mice protect the pancreas-derived β-cells from oxidative stress and increased insulin release from the beta cells of the pancreas in cultured RIN-5F cells. Also, decreased the level of serum of IL-6 and TNF-α in the diabetic mice. This suggests that the triterpenoids affect the serum insulin level and also may reduce insulin resistance by decreasing serum TNF-α. Conclusion: From these results, 1 and 2 are suggested to show anti-diabetic effect by stimulating insulin-dependent and by protecting pancreatic β-cells from oxidative stress and also may be an anti-obese, anti-insulin resistance and antihyperglycemic pro-drug.