The new technology of silkworm (Bombyx mori L.) artificial feed breeding has many characteristics and advantages.This study assessed silkworm rearing with mulberry leaf at all instars (MF) as the control, and used metabolomics to explore the differences in haemolymph metabolism of fifth instar silkworms under two modes of rearing with an artificial diet at all instars (AF) and rearing with an artificial diet during first to third instars and mulberry leaf during the fourth and fifth instars (AMF). The results show that, compared with silkworms of the MF group, the amount and fold change of various metabolites were higher in the haemolymph of AF group silkworms, and the metabolism of amino acids and uric acid, carbohydrates, lipids, and vitamins were changed. These changes may be the reasons for the poor performance of the AF silkworms. However, the amount and fold change of the various metabolites of silkworms in the AMF group were lower, and some metabolic pathways were more active. The amount of material and energy supply were greater. These changes could explain the high efficiency growth of body weight of silkworms after the conversion from artificial diet rearing to mulberry leaf rearing. These findings provide an important theoretical basis for the optimisation of artificial diet rearing technology for silkworms.