In this study, we evaluated the antidiabetic effect of a submerged culture of Ceriporia lacerata mycelium (CL01) on hematological indices, as well as protein and mRNA expression of the insulin-signaling pathway, in db/db mice. After CL01 was administrated for 4 weeks, blood glucose levels decreased consistently, and plasma insulin and c-peptide levels each decreased by roughly 55.8%, 40% of those in the negative control (p<0.05). With regard to HOMA-IR, an insulin resistance index, insulin resistance of the CL01-fed group improved over that of the negative control group by about 62% (p<0.05). In addition, we demonstrated that the protein expression levels of pIR, pAkt, pAMPK, and GLUT4 and the mRNA expression levels of Akt2, IRS1, and GLUT4 in the muscle cells of db/db mice increased in the CL01-fed group compared to the corresponding levels in the control group. These results demonstrate that CL01 affects glucose metabolism, upregulates protein and gene expression in the insulin-signaling pathway, and decreases blood glucose levels effectively by improving insulin sensitivity. More than 90% of those who suffer from type 2 diabetes are more likely to suffer from hyperinsulinemia, hypertension, obesity, and other comorbidities because of insulin resistance. Therefore, it is possible that CL01 intake could be used as a fundamental treatment for type 2 diabetes by lowering insulin resistance, and these results may prove be useful as basic evidence for further research into the mechanisms of a cure for type 2 diabetes.