Autophagy, a catabolic process responsible for the degradation of cytosolic components and the preservation of cellular homeostasis in virtually all eukaryotic organisms, is up-regulated when nutrient supplies are limited. However, whether early weaning induces autophagy in infants is not completely clear. In the present study, we used piglets as the early-weaning model to examine the autophagic activity in different tissues in response to nutrient status. Western blot analysis demonstrated that microtubule-associated protein 1 light chain 3-II, a promising marker protein for macroautophagy, was expressed at a notably higher level at 12 and 24 h weaning treatments than without weaning treatment (P < 0·01), and that the p62 (sequestome 1; SQSTM1) expression level was significantly attenuated after weaning treatments (P < 0·01) in the liver, spleen and skeletal muscle tissues. In addition, autophagic vacuoles detected by transmission electron microscopy were dramatically accumulated in these tissues (P < 0·01). Together, these results indicate that autophagy induced by early weaning may be helpful for the physiological system, which controls the balance of energy and nutrients for basic cell functions in the piglet model.