Herbs combination is a way to explore and develop traditional medicine in order to obtain additional benefits in the therapy of diseases.  Each  extract of Andrographis paniculata (Burm. F.) Wall ex Nees (AP) and Caesalpinia sappan Linn. (CS) where known as traditional herbs to help overcome diabetes mellitus. The study aimed to evaluate the safety of the hydroalcoholic extract (HE) combination of these herbs extract AP and CS in DDY mice. The HE dose of the combination extract used in this study are AP extract 200 mg and CS extract 150 mg. The mice are divided into 5 groups that will received suspending agent as a normal control and dose combination of 1,25 g/kg BW; 2,5 g/kg BW; 5 g/kg BW and 10 g/kg BW for each groups. Acute toxicity is evaluated through the determination of a LD50 in mice (up to 14 days). During the experiment, the effect on behavior, body weight, feed consumption are measured daily. Histology, hematology and biochemical parameters will be measured at the end of the study. After a 14-day treatment, the effect of HE will be observed the changes in some biochemical parameters. Histological examination of the liver, kidneys, lungs, heart, stomach, intestine and pancreas will be  observed after treatment to study the morphological changes.