In the present study, we found that the intraperitoneal injection of three main SCFAs had no significant effect on BW, FINS, and the blood lipid spectrum of T2D mice; however, SCFA treatment, especially butyrate, resulted in decreased RBG, FBG, and HOMA-IR, suggesting a positive effect of SCFAs on insulin sensitivity and glucose homeostasis by a nongastrointestinal interventional manner. The gene discussed is INS; the disease is type 2 diabetes mellitus.