Muscle contraction activates AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK1/2), two signaling molecules involved in the regulation of muscle metabolism. The purpose of this study was to determine whether activation of AMPK and/or ERK1/2 contributes to the regulation of muscle FA uptake and oxidation in contracting muscle. Rat hindquarters were perfused during rest (R) or electrical stimulation of increasing intensity by manipulating train duration (E1=25ms, E2=50ms, E3=100ms, E4=200ms). For matched FA delivery, FA uptake was significantly greater than R during E1, E2, and E3 (7.8±0.7 vs 14.4±0.3, 16.9±0.8, 15.2±0.5 nmolmin^-1g^-1 respectively, P<0.05), but not during E4 (8.3±0.3 nmolmin^-1g^-1, P>0.05). FA oxidation was significantly greater than R during E1 and E2 (1.5±0.1 vs. 2.3±0.2, 2.5±0.2 nmolmin^-1g^-1, P<0.05) before returning to resting levels for E3 and E4 (1.8±0.1 and 1.5±0.2 nmolmin^-1g^-1, P>0.05). A positive correlation was found between FA uptake and ERK1/2 phosphorylation from R to E3 (R²=0.55, P<0.05) and between FA oxidation and ERK1/2 phosphorylation from R to E2 (R²=0.76, P<0.05), correlations that were not maintained when the data for E4 and E3 and E4, respectively, were included in the analysis (R²=0.04 and R²=0.03, P>0.05). A positive correlation was also found between FA uptake and FA oxidation and AMPK activity for all exercise intensities (R²=0.57, R²=0.65 respectively, P<0.05). These results, in combination with previous data from our lab, suggest that ERK1/2 and AMPK are the predominant signaling molecules regulating FA uptake and oxidation during low to moderate intensity muscle contraction and during moderate to high intensity muscle contraction, respectively.