BACKGROUND Swietenia macrophylla King (Meliaceae) is used to treat diabetes mellitus in Malaysia. This study aims to evaluate the anti-hyperglycaemic potential of petroleum ether (PE), chloroform (CE) and methanol (ME) extracts of S. macrophylla seeds, in normoglycaemic and streptozotocin (STZ)-induced diabetic rats. METHODS Following treatment of normoglycaemic rats with S. macrophylla seed extracts, hypoglycaemic and intraperitoneal glucose tolerance tests (IPGTT) were performed, and blood glucose concentrations were measured. Similarly, glucose concentrations were measured after 1 and 14 days of extract treatment of STZ-induced diabetic rats. Glucose absorption by isolated everted intestine and glucose uptake by isolated abdominal muscle were tested after treatment with seed extracts. Gas chromatography mass spectrometry (GC-MS) analysis was performed on PE of S. macrophylla seeds to identify the compounds responsible for its activity. RESULTS None of the extracts had a significant effect on the blood glucose levels of 60 randomly selected normoglycaemic (normal) and diabetic rats undergoing hypoglycaemic tests. PE, however, significantly reduced blood glucose levels in 30 randomly selected normoglycaemic rats undergoing IPGTT tests 30-120 minutes after glucose administration. Repeated doses of 1000 mg/kg and 500 mg/kg PE to STZ-induced diabetic rats for 14 days did not reduce blood glucose levels significantly. PE did not significantly reduced the intestinal absorption of glucose, but significantly increased glucose uptake by abdominal muscle in the absence or presence of insulin. GC-MS analysis indicated that diterpenes, triterpenoids, fatty acid methyl esters, aldehydes and phytosterols may be responsible for the glucose lowering effects of PE. CONCLUSION PE extracts of S. macrophylla seeds showed anti-hyperglycaemic activity on IPGTTs . GC-MS analysis on the PE revealed that several compounds, including fucosterol and β-sitosterol, may be responsible for these anti-hyperglycaemic properties.