Diabetes mellitus (DM) is a multifactorial disease which is characterized by hyperglycemia, lipoprotein abnormalities and altered intermediary metabolism. The first insulin preparation can regulate glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. Insulin therapy has the longest history in the treatment of DM among other antidiabetic agents. The current study was followed the comparison of biochemical effects between Mixtard 30® (human natural insulin) and Novomix 30® (synthetic insulin) after two weeks. eighty male albino rats (200-220 gm). They were randomly divided into four groups. First group conserved as control group. The other groups received STZ (100 mg/kg body weight) to become diabetic. The second group conserved as diabetic, the third group treated with a Mixtard 30® (55 IU/kg body weight/day). The fourth group treated with Novomix 30® (55 IU/kg body weight/day) for two weeks. The results indicated that STZ diabetes caused significant increases in blood glucose, HbA1c, hematological parameters (WBCs, lymphocyte and PLT), ALT, CRP, Creatinine, total Cholesterol and TG and decreased in RBCs, Hb, HCT, MCV and MCHC and body weight when compared to control -ve group. The Mixtard 30® and Novomix 30® improved these results, there was no statistical difference in mean biochemical results between Mixtard 30® and Novomix 30® as treatments of diabetes.