Catharanthus roseus is a traditional medicinal plant that contains the active compound which is very important for health. The plant has been proven to significant source of bioactive compounds as chemotherapeutic agents. This study aims to determine the activity of various extracts consentration of Chatarantus roseus against a-glucosidase enzyme inhibitory, which is potentially as antihyperglicemic. Catharanthus roseus extracted using six different solvents namely, hexane, methanol, ethyl acetate, buthanol and water. All the extracts was determined for inhibition of a-glucosidase enzyme. Effect of the extract on antihyperglycemic activity was determined using 20 rats. The animals was randomly divided into four groups. Each group contains five animals. Group I: rats normal; group II: rats normal and Catharantus roseus methanol extract of 1% w/v (1 cc/200g bw/day), group III: hyperglycemic rats; and group IV hyperglycemic rats and Catharantus roseus methanol extract of 1% w/v (1 cc/200g bw/day). The treatment was conducted for 8 days. The parameters were tested of blood glucose levels and profiles of GLUT4 in Gastrocnemius muscle. The results showed that the hexane and methanol extract at dose of 25 ppm have inhibition of a-glucosidase activity with concentration of inhibitor to inhibit 50% of its activity (IC50) of 187.93 and 348.29, respectively, while other extracts had no activity. Furthermore, the methanol extracts have activity reduce of blood glucose levels in rats under conditions of hyperglycemia. The immunohistochemical staining on muscle of experimental rats showed that treatment with methanol extract led to the expression of GLUT4 appears brown color intensity is stronger than the other treatments.