Diabetes is a major threat to global public health that is rapidly getting worse, and the biggest impact is on adults of working age in developing countries. At least 171 million people worldwide have diabetes. This figure is likely to be more than double by year 2030 to reach 366 million Diabetes mellitus is a multifactorial disease that can have significant impact on health, quality of life, and life expectancy of individuals, as well as on the health-care system. Consequently, the present study has been intended to through more light on such issue and to evaluate and compare the therapeutic role of glimepiride as a chemical drug and Nerium oleander extract as an herbal medicine in diabetic rats. Further research is needed to test antidiabetic activity of other herbs as natural products probably have little or no side effect compared to synthetic drugs.