Previous studies have shown that chronic salt overload increases insulin sensitivity, while chronic salt restriction decreases it. In the present study we investigated the influence of dietary sodium on: a) GLUT4 gene expression, by Northern and Western blotting analysis; b) in vivo GLUT4 protein translocation, by measuring the GLUT4 protein in plasma membrane and microsome, before and after insulin injection; c) insulin signaling, by analyzing basal and insulin-stimulated tyrosine phosphorylation of IR-, IRS-1 and IRS-2. Wistar rats were fed normal (NS-0.5 %), low (LS-0.06 %) or high (HS-3.12 %) sodium diets for 9 weeks, and were sacrificed under pentobarbital anesthesia. Compared to NS, HS rats increased (P<0.05) the GLUT4 protein in adipose tissue and skeletal muscle, whereas GLUT4 mRNA was increased only in adipose tissue. GLUT4 expression was unchanged in LS rats compared to NS rats. The GLUT4 translocation in HS rats was higher (P<0.05) both in basal and insulin-stimulated conditions. On the other hand, LS rats did not increase the GLUT4 translocation after insulin stimulus. Compared to NS rats, LS rats showed reduced (P<0.01) basal and insulin-stimulated tyrosine phosphorylation of IRS-1 in skeletal muscle and IRS-2 in liver; whereas HS rats showed enhanced basal tyrosine phosphorylation of IRS1 in skeletal muscle (P<0.05) and of IRS-2 in liver. In summary, increased insulin sensitivity in HS rats is related to increased GLUT4 gene expression, enhanced insulin signaling and GLUT4 translocation; whereas decreased insulin sensitivity of LS rats does not involve changes in GLUT4 gene expression, but is related to impaired insulin signaling.