The following results were obtained: (1) the downregulation of SK2 protein and the upregulation of SK3 protein occurred in the atria of T2DM rats compared with the control group; (2) PKC/ERK signaling pathway mediated the downregulation of SK2 protein and the upregulation of SK3 protein; (3) long-term metformin reversely regulated the expression of SK2 and SK3 proteins through PKC/ERK signaling pathway. Here, KCNN3 is linked to type 2 diabetes mellitus.