Objective To explore the establishment methods of rat models of diabetes mellitus by streptozotocin combined with different diets and to assess the learning and memory ability of the rat models, and to provide reliable models for diabetes research and related drug development. MethodsSeventy male Sprague-Dawley rats were randomly divided into 7 groups, (10 rats each):the normal group (I), high fat diet group (II), 0 week STZ (30 mg/kg) + high fat diet group (III), 0 week STZ (30 mg/kg) + standard diet group (IV), 6 weeks STZ (20 mg/kg) + high fat diet group (V), 6 weeks STZ (25 mg/kg) + high fat diet group (VI) and 6weeks STZ (30 mg/kg) + high fat diet group (VII). Diabetic models were established by intravenous injection of STZ, combined with different diets. The blood glucose (BG) levels were continuously monitored. Biochemical methods were employed to detect the serum lipids. The levels of serum insulin and glucagon were also determined. Morris water maze was used to test the changes of learning and memory ability in the model groups. ResultsCompared with the control, the blood glucose level in the rats of group III was significantly increased 72 h after STZ injection and reached to a peak 2 weeks after STZ injection (P<0.01). Then it decreased gradually, the BG remained at a level of 15 mmol/L 10 weeks after STZ injection (P<0.05). The BG value of the rats in the group IV was increased 72 hours after STZ injection, then it decreased rapidly, and dropped to a normal level 10 weeks after STZ injection. The BG values of rats in the groups V, VI and VII were elevated after the STZ injection and displayed a fluctuating profile in the following period. The range of BG changes depended to the dose of STZ. Compared with the control group, the values of insulin levels of the groups III, IV and V were increased after high fat feeding for 10 weeks. The values of glucagon in all experimental groups were increased except the group VI. The values of CHO, TG, LDL-c were increased in all high fat diet-fed rats. Morris water maze test results showed that the escape latency of group VII was significantly longer than that in the control group. ConclusionsOur findings indicate that intravenous injection of STZ (30 mg/kg) with high fat diet is a rapid and stable method for establishing a diabetic model in rats. Indeed, after 6 weeks of high fat diet and subsequent STZ (30 mg/kg) injection, the rats tend to develop type 1 diabetes since they exhibit a high level of blood glucose and low insulin level in the rat models.