Background: A poor-quality diet may contribute to chronic levels of inflammation and alter susceptibility to pain via activation of immune cells. Methods: Here we examined the effect of a human-relevant Standard American Diet (SAD) prior to and following peripheral inflammatory injury. Results: SAD consumption significantly increased Iba-1 staining in the dorsal horn of the spinal cord in rats in the presence and absence of peripheral inflammatory injury. Conclusions: These data suggest that diet may predispose animals to an exacerbated immune response in the both presence and absence of injury. Diet may extend recovery times as a consequence of persistent immune cell activation and enhanced responses to injury.