Various nature-mimicking pyranones such as 6-(2,5-dimethylfuran-3-yl)-pyran-2-one and 6-(furan-2-yl)-pyran-2-one derivatives were synthesized and evaluated for their in vivo antihyperglycemic activity in sucrose-loaded streptozotocin-induced diabetic rat model. Five of the test compounds showed significant lowering of plasma glucose level in STZ-S model.