Obesogenic effect of high-fat (HF) diet is counterbalanced by stimulation of energy expenditure and lipid oxidation in response to the meal. Aim of this study was to reveal whether muscle nonshivering thermogenesis could be stimulated by HF diet, especially in obesity-resistant A/J as compared with obesity-prone C57BL/6J (B/6J) mice. Experiments were performed on male mice born and maintained at 30 °C. Four-week-old mice were randomly weaned onto a low-fat (LF) or HF diet for 2 weeks. In the A/J LF mice, cold exposure (4 °C) resulted in hypothermia, while the A/J HF, B/6J LF and B/6J HF mice were cold-tolerant. Cold-sensitivity of the A/J LF mice was associated with a relatively low whole-body energy expenditure under resting conditions, which was normalized by HF diet. In both strains, HF diet induced uncoupling protein 1-mediated thermogenesis, with a stronger induction in A/J mice. Only in A/J mice: (i) HF diet augmented activation of whole body lipid oxidation by cold; and (ii) at 30 °C, oxygen consumption, total content and phosphorylation of AMP-activated protein kinase (AMPK), and AICAR-stimulated palmitate oxidation in soleus muscle was increased by HF diet in parallel with significantly increased leptinemia. Gene expression data in soleus muscle of the A/J HF mice indicated a shift from carbohydrate to fatty acid oxidation. Our results suggest a role of muscle nonshivering thermogenesis and lipid oxidation in the obesity-resistant phenotype of A/J mice and indicate that HF diet could induce thermogenesis in oxidative muscle, possibly via the leptin-AMPK axis.