Objective To evaluate the rat model of type 2 diabetes mellitus (T2DM) associated with depression by body weight, fasting blood glucose, manifestations, and open field test. Methods The T2DM rat model was induced by high fat diet and low dose of STZ injection, and in addition, the T2DM rats were made restraint stress for 21 days. 32 Wistar rats were randomly divided into three groups: normal group (group N), T2DM group (group T) and T2 DM with depression group (group T+D), with 8 rats in each group. After the model was established, to measure the body weight, fasting blood glucose at day 0, 7, 14, and 21, and observe the gross manifestations, drinking and diet, feces, urine, and mental state, and test the rat depression by open field test. Results After establishment of the T+D rat model, the rats in group T+D showed some symptoms, including messy dark and gloomy hair, slow movement, increasing drinking, diet, feces and urine and mental fatigue. At day 0, 7, 14, and 21, compared with the group N, the body weight of the group T and group T+D were decreased, showing a significant difference (P<0.05;P<0.01). At day 0, 7, 14, and 21, compared with the group N, and the fasting blood glucose in the groups T and T+D were increased, with a significant difference (P<0.01). After 21 days of restraint stress, the fasting blood glucose in the group T+D was significantly higher than that in the group T (P<0.01). Compared with the group N, the total movement distance in 5 minutes in the group T+D was reduced, but without a significant difference (1532.6±126.8 cm vs. 940.5±208.3 cm, P>0.05). Compared with the group N, the movement speed in 5 minutes in the group T was significantly slower than that in the group T, with a significant difference (5.1±0.4 cm/s vs. 2.9±0.6 cm/s, P<0.05), and even more slower than that in the group T+D, with a significant difference (5.1±0.4 cm/s vs. 2.4±0.5 cm/s, P<0.01). Conclusions A rat model of type 2 diabetes mellitus associated with depression has been successfully established by high fat diet and injection of low dose streptozotocin in combination with restraint stress for 21 days. This rat model is useful for further relevant studies.