Although several neural pathways have been implicated in feeding behaviors in mammals, it remains unclear how the brain coordinates feeding motivations to maintain a constant body weight (BW). To gain insight into this issue, we sought to identify a neural pathway that functions critically in regulation of BW and food intake using Drosophila. To do so, we performed a genetic screen on a collection of neuropeptide GAL4 driver lines expressing a neural silencer using a series of quantitative assays measuring BW and food intake. In our recent study, we reported the identification of a neuropeptide pathway important for BW control via inducing satiety in Drosophila. Silencing of myoinhibitory peptide (MIP) neurons significantly increased BW through augmented food intake and fat storage. Likewise, the loss-of function mutation of mip also increased feeding and BW. Suppressing the MIP pathway induced satiated flies to behave like starved ones, with elevated sensitivity toward food. Conversely, activating MIP neurons greatly decreased food intake and BW and markedly blunted the sensitivity of starved flies toward food. Upon terminating the activation protocol of MIP neurons, the decreased BW reverts rapidly to the normal level through a strong feeding rebound, indicating the switch-like role of MIP pathway in feeding. Surprisingly, the MIP-mediated BW decrease occurred independently of sex peptide receptor (SPR), the only known receptor for MIP, suggesting the presence of a yet-unknown MIP receptor. Together, our results reveal a novel anorexigenic pathway that controls satiety in Drosophila and provide a new avenue to study how the brain actively maintains a constant BW.