To identify the best reference genes, this study systematically evaluates the stability of eleven candidate reference genes, including ACT, B2M, GAPDH, HPRT1, PPIA, RPL13A, RPLP0, TBP, UBC, YWHAZ, and 18SRNA, in liver, pancreas, and both types of tissues across four mouse groups of control, obesity, STZ-induced diabetic and treated STZ-diabetic groups. This evidence concerns the gene HPRT1 and obesity due to melanocortin 4 receptor deficiency.