Heat stress causes morbidity and mortality in humans and animals and threatens food security by limiting livestock productivity. Inflammatory signaling may contribute to heat stress-mediated skeletal muscle dysfunction. Previously we discovered increased circulating endotoxin and intramuscular oxidative stress and TNFα protein abundance but not inflammatory signaling following 24 and 72 hours of heat stress. Thus, the purpose of this investigation was to clarify the role of inflammatory signaling in heat stressed skeletal muscle. Crossbred gilts (n=8/group) were assigned to either thermal neutral (24° C), heat stress (37° C), or pair-fed thermal neutral (24° C) conditions for 12 hours. Following treatment, animals were euthanized and the semitendinosus red (STR) and white (STW) were recovered. Heat stress did not alter inflammatory signaling in STW. In STR, relative heat shock protein abundance was similar between groups as was nuclear content of HSF1. In whole homogenate, relative abundance of the NF-B activator IKKα was increased by heat stress though abundance of NF-B was similar between groups. Relative abundance of phosphorylated NF-B was increased by heat stress in nuclear fractions. AP-1 signaling was similar between groups. While there were few differences in transcript expression between thermal neutral and heat stress, 80 and 56% of measured transcripts driven by NF-B or AP-1, respectively, were increased by heat stress compared to pair-fed thermal neutral. Heat stress also caused a reduction in IL-6 transcript and relative protein abundance. These data demonstrate that short-term heat stress causes inflammatory signaling through NF-B in oxidative, but not glycolytic, skeletal muscle.