Abstract: Objective:The objective of this work was to explore the hypoglycemic effects of D-pinitol compound with Mn²⁺ on type 2 diabetes mellitus rats and underling mechanism. Methods:A model of type 2 diabetes mellitus(T2DM)was established by feeding high-fat diet and streptozocin(STZ)injecting to male rats. The rats were divided into the normal group,control group,positive control group,D-pinitol group,low,medium and high complex Mn²⁺ group.Body weight and fasting blood glucose(FBG)were tested each week. Oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)was tested after four-week-treatment. The contents of glycated serum protein(GSP)and fasting insulin(FINS)were determined after five-week-treatment and insulin sensitivity index(ISI)and pancreatic β cell function index(HOMA-β)were calculated. The expression of AMPK genes was detected with real-time polymerase chain reaction(real-time PCR). Results:Compared with the model group,the hypoglycemic effects of dosage groups increased significantly(p<0.05),and the high combined group increased significantly(p<0.01).Compared with the D-pinitol group,the FINS and GSP of the high combined group increased significantly. Compared with the model group,the mRNA expression levels of ISI-1,ISI-2 and AMPKα-2 increased significantly(p<0.05),and the high combined group increased significantly(p<0.01).The mRNA expression levels of AMPKα-1 and GLUT4 increased significantly(p<0.05)while PGC-1α,PEPCK and G6pase mRNA expression decreased significantly(p<0.05)in the high combined group. Conclusion:D-pinitol compound with Mn²⁺ could improve the body’s sensitivity to insulin,moreover,it has a positive effect on hypoglycemic activity through AMPK signaling pathway.