Hyperglycemia is recognized as the primary indicator of diabetes. The occurrence of Hyperglycemia results from a combination of contributing factors, such as dietary habits, exercise routines, and overall lifestyle choices. Accumulating evidence showed the hyperglycemia also causes inflammation, which changes the body's cellular and immune systems. Similarly, the acute hyperglycemia increases the levels of pro-inflammatory cytokines such as TNF-α and IL-6. The present study aimed to determine the effect of Muntingia calabura leaves extracts administration toward the immune system in hyperglycemia-induced high-fat diet in mouse model. Five experimental groups were applied in this study, including the control group, hyperglycemic group, and three groups treated with M. calabura leaves extracts in several doses such as 400, 700, and 2800 mg/kg BW. Flow cytometry analysis was performed to evaluate the inflammation markers such as IL-1β, IFN-ɣ, or TNF-α on the subset of macrophages and Th1 cells. Our findings indicate that the extracts did not enhance or elevate the production of IL-1β by the macrophage subgroup/population. Similarly, the pro-inflammatory cytokines such as IFN-ɣ and TNF-α were reduced on the CD4 after treated with the extracts. Therefore, this study demonstrated that M. calabura leaves extracts exerts suppressive activity to maintain the physiological level of immune system. To be highlighted, the immunosuppression action reduced several inflammatory markers, including macrophages and Th1 cells. Thus, the present study suggested that M. calabura leaves extracts possibly become alternative and complementary medicine against hyperglycemia.