Diabetes mellitus is the most common human disease and there is growing interest for plant based therapy in managing diabetes mellitus specifically in the developing world. In the present study, Rhazya stricta Decne extract was analysed for its antidiabetic activities. Crude methanolic extracts of different plant parts were tested in vivo on albino mice Balb-C, for the reduction of blood glucose, urea, cholesterol, triacylglycerides and glycosylated haemoglobin. Results obtained showed that leaves of R. stricta have best antidiabetic effect by reducing blood glucose level, Glycosylated haemoglobin, triacylglycerides and Cholesterol in hyperglycaemic mice. The R. stricta leaves extract being most active was further fractionated by solvent extraction using n- Hexane, ethyl acetate, chloroform and water and all fractions were tested for same activities. It was found that ethyl acetate fraction is most effective in the reduction of blood glucose level at fasting and random conditions and blood glucose reduction was comparable to Glucophage, a standard antidiabetic drug. The present study suggests that Rhazya stricta leaves extract and its ethyl acetate fraction has great potential for development of antidiabetic drug.DOI: http://dx.doi.org/10.3329/icpj.v4i2.21484 International Current Pharmaceutical Journal, January 2015, 4(2): 353-361