The study was initiated to determine the antidaibetic activity of Syzygium calophyllifolium in Streptozotocin-Nicotinamide (STZ-NA) induced diabetic rats. The rats were treated with 100 and 200mg/kg of the Syzygium calophyllifolium bark methanol extract (SCBM) and compared with the diabetic, normal and standard glibenclamide groups. The blood glucose level and body weight of the rats in different groups were monitored at regular intervals. The serum, blood biochemical and histopathological parameters of liver, kidney and pancreas were also analyzed. In vivo antioxidants like SOD, CAT, GST, GSH and GR levels were estimated in liver and kidney. SCBM (100mg/kg) extract could reduce the blood glucose level from the 15th day itself (213.67mg/dL) and the best reduction was observed till the end of the study with 259.25mg/dL (200mg/kg). Initial decrease in body weight was recovered after drug treatment and an increase in body weight was observed on the 4th week. The haematological parameters like total haemoglobin, packed cell volume percentage, total WBC and RBC content were found normal compared to that of normal untreated rats. Glibenclamide was also equally effective. The higher dose of SCBM extract could normalize the triglycerides, HDL, cholesterol and VLDL constituents in blood serum to the levels almost similar to that of normal rats. The results of the in vivo antioxidant levels showed that there are no significant difference in SOD, GSH and GR levels in all the groups compared to the normal control. SCBM and SMBM at 200mg/kg dose were much effective over the lower dose. The histology revealed that SCBM 200mg/kg could protect the cellular architecture of liver kidney and pancreas. The results from the study confirm ethnopharmacological significance of the plant and could be taken further for the development of an effective pharmaceutical drug against diabetes.