Male heterozygous TG(mREN2)27 rats (TGR) overexpress a murine renin transgene, display marked hypertension, and have insulin resistance of skeletal muscle glucose transport and insulin signaling. We have shown previously that voluntary exercise training by TGR rats improves insulin-mediated skeletal muscle glucose transport. The present study evaluated whether this training-induced enhancement of muscle glucose transport is associated with upregulation of critical insulin signaling elements, including insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3-kinase), Akt, and glycogen synthase kinase-3 (GSK-3). TGR rats remained sedentary or ran spontaneously in activity wheels for six weeks, averaging 7.1 ± 0.8 km/d by the end of week 3 and 4.3 ± 0.5 km/d over the final week of training. Exercise training reduced total abdominal fat by 20% (P<0.05) in TGR runners (2.64 ± 0.01% of body weight) compared to sedentary TGR controls (3.28 ± 0.01%). Insulin-stimulated (2 mU/ml) glucose transport activity in soleus muscle was 36% greater in TGR runners compared to sedentary TGR controls. However, the protein expression and functionality of tyrosine phosphorylation of IR and IRS-1, IRS-1 associated with the p85 regulatory subunit of PI3- kinase, and ser⁴⁷³ phosphorylation of Akt were not altered by exercise training. Only insulinstimulated GSK-3 ser⁹ phosphorylation was increased (22%) by exercise training. These results indicate that voluntary exercise training in TGR rats can enhance insulin-mediated glucose transport in skeletal muscle, as well as reduce total abdominal fat mass. However, this adaptive response in muscle occurs independently of modifications in the proximal elements of the insulin signaling cascade.