IL-6 is a biologically active substance which appears to be involved in regulating skeletal muscle lipid oxidation. Ablation of IL-6 (IL-6(-/-)) may therefore be expected to increase intracellular lipid accumulation, possibly via a concurrent increase in fatty acid transporters such as FAT/CD36 and FABPpm. This however may only occur in oxidative muscles which utilize fatty acids at a greater rate than glycolytic muscles. In the present study we examined the fatty acid transporter protein expression as well as the lipid content and profiles of free fatty acids (FFA), diacylglycerols (DGs) and triacylglycerols (TGs) in skeletal muscles of IL-6 deficient mice at 4 and 12 months of age. FAT/CD36 and FABPpm protein content was increased in red muscles in IL-6(-/-) mice compared to WT mice at 4 (RG) and 12 months (soleus and RG). Along with this, FFA, DG and TG concentrations were also increased in these red IL-6(-/-) muscles. In addition, the IL-6(-/-) genotype increased the saturated FA acid composition of the intramuscular TG fraction. In contrast, in white gastrocnemius muscle the IL-6(-/-) genotype has no effect on the expression of fatty acid transporters as well as the lipid content and composition at either 4 mo or 12 months of age. IL-6 ablation increases fatty acid transporter expression and intramuscular lipid accumulation, particularly the saturated fatty acids. These effects however were confined to oxidative muscles, as glycolytic muscles were not affected.