Objective To observe the effect of trigonelline, Fructus Schisandrae oil and Metformin therapy on neuritin expression in hippocampal area and glucose and lipid metabolisms in rats with type 2 diabetes. Methods Type 2 diabetic rat model was established by feeding Streptozotocin plus high-sugar and high-lipid diet. The diabetic rats were divided into diabetic model group, combined drug treatment group and Rosiglitazone group with 11 rats in each group. The rats received continuous treatment for 8 weeks. The normal control group consisted of 10 normal SD rats. FBG, HbA1c, TC, FINS, TG, liver glycogen and muscle glycogen levels were tested. Real-time PCR and Western blot were used to determine neuritin expression level in hippocampus. Results Compared with the normal control group, the FBG, HbA1c, FINS, TC and TG levels were increased significantly; the insulin sensitivity index (ISI), liver glycogen and muscle glycogen levels, hippocampal neuritin mRNA and protein expressions were decreased significantly in the diabetic model group after treatment for 8 weeks (P < 0.01). Compared with the diabetic model group, the FBG, HbA1c and FINS levels were significantly decreased; but ISI, liver glycogen and muscle glycogen levels, and the expression levels of hippocampal neuritin mRNA and protein were significantly increased in the combined drug treatment group and Rosiglitazone group (P < 0.01). Compared with the diabetic model group, TC and TG decreased significantly in the combined drug treatment group (P < 0.01); but there were no significant differences in TC or TG between the diabetic model group and the Rosiglitazone group (P > 0.05). Conclusions Combined trigonelline, Fructus Schisandrae oil and Metformin therapy can improve glucose and lipid metabolisms and expression of neuritin in the hippocampus of type 2 diabetic rats.