The objective of this study was to determine how an ATP-sensitive K⁺ (K_ATP) channel deficiency affects the contractile and fatigue characteristics of extensor digitorum longus (EDL) and soleus muscle of 2- to 3-mo-old and 1-yr-old mice. K_ATP channel-deficient mice were obtained by disrupting theKir6.2 gene that encodes for the protein forming the pore of the channel. At 2–3 mo of age, the force-frequency curve, the twitch, and the tetanic force of EDL and soleus muscle of K_ATPchannel-deficient mice were not significantly different from those in wild-type mice. However, the tetanic force and maximum rate of force development decreased with aging to a greater extent in EDL and soleus muscle of K_ATP channel-deficient mice (24–40%) than in muscle of wild-type mice (7–17%). During fatigue, the K_ATP channel deficiency had no effect on the decrease in tetanic force in EDL and soleus muscle, whereas it caused a significantly greater increase in resting tension when compared with muscle of wild-type mice. The recovery of tetanic force after fatigue was not affected by the deficiency in 2- to 3-mo-old mice, whereas in 1-yr-old mice, force recovery was significantly less in muscle of K_ATP channel-deficient than wild-type mice. It is suggested that the major function of the K_ATP channel during fatigue is to reduce the development of a resting tension and not to contribute to the decrease in force. It is also suggested that the K_ATP channel plays an important role in protecting muscle function in older mice.