The present study was designed to investigate the hypoglycemic effects of D and L isomers of glutamic acid in diabetic rats through inhibiting phosphoenolpyruvate carboxykinase. The results of this in vitro study showed meaningful inhibitory effects by glutamic acid isomers to phosphoenolpyruvate carboxykinase activity. Groups of 10 rats were used as control and treated groups. Diabetes in experimental rats was induced by administrating sterptozotocin (STZ) (60 mg kg-1, i.p., once). The effect of L and D glutamic acids on blood glucose was studied by injecting doses of 100 mg kg-1 b.wt. intra peritoneally to groups of diabetic and control rats. Present results showed that the D isomer of glutamic acid causes a significant decrease in blood glucose 1.5 h post-injection with continued activity up to 4 h. The L isomer as previously reported resulted in hyperglycemia, probably because of its involvement as a precursor in the gluconeogenesis pathway. Following up the changes in serum protein, urea and triglyceride concentration we observed no significant alterations in their concentrations indicating no side effects for D-glutamic. We found evidences that D- glutamic acid may be considered for further pharmaceutical experiments as a hypoglycemic drug.